Generation of cells with phenotypes of both intercalated duct-type and myoepithelial cells in human parotid gland adenocarcinoma clonal cells grown in athymic nude mice

A neoplastic epithelial cell line was established from nude mice tumors grown after transplantation of surgical specimens from a human parotid gland adenocarcinoma. This cell line, which had ultrastructure similarities to salivary intercalated duct cells, was found by immunohistochemical techniques to contain amylase, but myosin was not detected. Ultrastructurally, cells of an intermediate type between intercalated ductal and myoepithelial cells were found in the transplanted tumors. Moreover, the expression of myosin in addition to the presence of amylase was detected in the tumors. These findings indicate that some transplanted tumor cells appear to be differentiating towards myoepithelial cells.     

Immunohistochemical demonstration of lysozyme and lactoferrin in salivary pleomorphic adenomas

Immunohistochemical identification of lysozyme and lactoferrin was made in salivary pleomorphic adenomas (147 cases) and the staining patterns were evaluated with respect to the histological features and histogenesis. In normal salivary glands, the intercalated duct cells gave positive staining for lysozyme in major glands, and serous acinar cells, demilune cells, and interlobular duct cells were positive in minor glands. Lactoferrin staining was irregularly positive in serous cells and ductal epithelium. In pleomorphic adenomas, the reaction for lysozyme was positive in 14% (21/147) of the cases, and was confined to luminal cells of tubulo-ductal structures. Lactoferrin in pleomorphic adenomas was distributed in luminal tumor cells (51%; 75/147), in outer tumor cells (3%; 4/147), and in both luminal and outer tumor cells (5%; 7/147) in tubulo-ductal structures; it was also detected in plasmacytoid myoepithelial cells (5%, 8/147). However, modified myoepithelial cells and other types of neoplastic myoepithelial participants were negative for lactoferrin staining. The occurrence of both lysozyme and lactoferrin in salivary pleomorphic adenomas suggests their participation in the local defense mechanism in the tumor.     

An ultrastructural study of the submandibular glands of the squirrel monkey, Saimiri sciureus

In squirrel monkey (Saimiri sciureus) the position of submandibular glands in the neck, on either side of the trachea, more closely resembles that of rodents than that of other primates. The glands exhibit seromucous acini and mucous tubules with seromucous demilunes. Electron microscopy shows basal cytoplasmic folds and well-developed intercellular tissue spaces and canaliculi only in relation to seromucous cells. Greatly dilated cisternae of the granular endoplasmic reticulum and prominent Golgi membranes are characteristic of the mucous cells. The secretory granules of seromucous and mucous cells are morphologically distinct and indicate chemically different products for the two cell types. Histochemically, the seromucous cell shows the presence of acid mucosubstance as indicated by the PAS and Alcian blue techniques. Preliminary studies showed no appreciable quantity of amylase in submandibular glands. The intercalated duct cell is juxtaposed with the acinar cell or mucous tubule cell. Short luminal microvilli, prominent Golgi complexes and scant apical granules are notable features of intercalated duct cells. Four cell types compose the striated ducts, viz., granular light cells, agranular dark cells, vesiculated dark cells, and basal cells. Peripheral nerves are found in five different locations: in the connective tissue (interstitial), between adjacent myoepithelial and mucous-secreting cells, in the intercellular space between adjacent secretory cells, and between basal plications of striated ducts and between adjacent myoepithelial and intercalated duct cells.     

Label-retaining cells in the rat submandibular gland.

To identify stem cells in salivary glands, label-retaining cells (LRCs) were established in rat submandibular glands. Developing and regenerating glands were labeled with bromodeoxyuridine (BrdU). To cause gland regeneration, the glands were injured by duct obstruction. BrdU LRCs were observed in all the parenchymal structures except for the acinus of the glands labeled during regeneration. Among these LRCs, a few, but not many, expressed neither keratin18 (K18; an acinar/duct cell marker) nor alpha-smooth muscle actin (alphaSMA; a myoepithelial cell marker), and thus were putative stem cells. These (K18 and alphaSMA)(neg) LRCs were invariably observed in the intercalated duct and the excretory duct. In the intercalated duct, they were at the proximal end bordering the acinus (the neck of the intercalated duct). Next, to test the above identification, gland extirpation experiments were performed. LRCs were established by labeling developing glands with iododeoxyuridine (IdU) in place of BrdU. Removal of one submandibular gland forced the IdU-LRCs in the remaining gland to divide. They were labeled with chlorodeoxyuridine (CldU). The (K18 and alphaSMA)(neg) LRCs in the neck of the intercalated duct and in the excretory duct did not change in number or in IdU label. The CldU label appeared in these cells and then disappeared. These results indicate that the (K18 and alphaSMA)(neg) LRCs have divided asymmetrically and are thus considered salivary gland stem cells.     

Multiple expression of keratins, vimentin, and S-100 protein in pleomorphic salivary adenomas.

Immunohistochemical staining for S-100 protein and the intermediate filaments keratin and vimentin, was made in 41 salivary adenomas. In pleomorphic adenomas, great heterogeneity in the staining, as well as multiple and co-expressions of these proteins were found in the outer tumor cells of tubulo-ductal structures and modified myoepithelial cells, but not in the luminal tumor cells. All the outer tumor cells stained for S-100 protein, 97% for K8.12 keratin and 85% for vimentin. Of these cells, 29% showed multiple expression of K8.12 keratin, vimentin, and S-100 protein, and 17% showed co-expression of K8.12 and S-100 protein. Modified and neoplastic myoepithelial cells showed similar expressions of these proteins to those of outer tumor cells; myoepithelioma cells displayed the most complicated pattern, being positive for KL1, PKK1, and K8.12 keratins, vimentin and S-100 protein. In luminal tumor cells there was a heterogeneous expression of KL1 and PKK1 in 82%, and of KL1, PKK1, and K8.12 in only 14.7%. Based on the immunohistochemical findings obtained with different monoclonal antibodies in pleomorphic salivary adenomas, outer tumor cells may be derived from ductal basal cells and luminal tumor cells from intercalated duct cells.     

Multiple expression of keratins,vimentin, and S-100 protein in pleomorphic salivary adenomas

Immunohistochemical staining for S-100 protein and the intermediate filaments keratin and vimentin, was made in 41 salivary adenomas. In pleomorphic adenomas, great heterogeneity in the staining, as well as multiple and co-expressions of these proteins were found in the outer tumor cells of tubulo-ductal structures and modified myoepithelial cells, but not in the luminal tumor cells. All the outer tumor cells stained for S-100 protein, 97% for K8.12 keratin and 85% for vimentin. Of these cells, 29% showed multiple expression of K8.12 keratin, vimentin, and S-100 protein, and 17% showed co-expression of K8.12 and S-100 protein. Modified and neoplastic myoepithelial cells showed similar expressions of these proteins to those of outer tumor cells; myoepithelioma cells displayed the most complicated pattern, being positive for KL1, PKK1, and K8.12 keratins, vimentin and S-100 protein. In luminal tumor cells there was a heterogeneous expression of KL1 and PKK1 in 82%, and of KL1, PKK1, and K8.12 in only 14.7%. Based on the immunohistochemical findings obtained with different monoclonal antibodies in pleomorphic salivary adenomas, outer tumor cells may be derived from ductal basal cells and luminal tumor cells from intercalated duct cells.     

双丁酰环磷酸腺苷耐人肝癌细胞株SMMC－7721表面N－糟链类型及天线数的影响

本文采用系列凝集素柱层析法,并配合外切精苷酶研究了在双丁酰环磷酸腺苷（ｄＢ－ｃＡＭＰ）作用１～５天过程中人肝癌细胞株ＳＭＭＣ－７７２１细胞表面Ｎ－糖链类型及复杂型糖链天线数的变化。结果表明,ｄＢ－ｃＡＭＰ促进３Ｈ—Ｍａｎ参入细胞表面Ｎ－糖链,使高甘露糖型Ｎ－糖链的百分比下降,并促进二天线Ｎ－糖链的生物合成。使多天线特别是四天线和Ｃ２Ｃ２Ｃ６三天线Ｎ－糖链的百分比减少．结果提示,Ｎ－糖链结构的这些变化可能是ｄＢ－ｃＡＭＰ诱导ＳＭＭＣ－７７２１细胞向正常方向分化的结果。     

Immunocytochemistry of myoepithelial cells in the salivary glands

MECs are distributed on the basal aspect of the intercalated duct and acinus of human and rat salivary glands. However, they do not occur in the acinus of rat parotid glands, and sometimes occur in the striated duct of human salivary glands. MECs, as the name implies, have structural features of both epithelial and smooth muscle cells. They contract by autonomic nervous stimulation, and are thought to assist the secretion by compressing and/or reinforcing the underlying parenchyma. MECs can be best observed by immunocytochemistry. There are three types of immunocytochemical markers of MECs in salivary glands. The first type includes smooth muscle protein markers such as -SMA, SMMHC, h-caldesmon and basic calponin, and these are expressed by MECs and the mesenchymal vasculature. The second type is expressed by MECs and the duct cells and includes keratins 14, 5 and 17, 1β1 integrin, and metallothionein. Vimentin is the third type and, in addition to MECs, is expressed by the mesenchymal cells and some duct cells. The same three types of markers are used for studying the developing gland.

Development of MECs starts after the establishment of an extensively branched system of cellular cords each of which terminates as a spherical cell mass, a terminal bud. The pluripotent stem cell generates the acinar progenitor in the terminal bud and the ductal progenitor in the cellular cord. The acinar progenitor differentiates into MECs, acinar cells and intercalated duct cells, whereas the ductal progenitor differentiates into the striated and excretory duct cells. Both in the terminal bud and in the cellular cord, the immediate precursors of all types of the epithelial cells appear to express vimentin. The first identifiable MECs are seen at the periphery of the terminal bud or the immature acinus (the direct progeny of the terminal bud) as somewhat flattened cells with a single cilium projecting toward them. They express vimentin and later -SMA and basic calponin. At the next developmental stage, MECs acquire cytoplasmic microfilaments and plasmalemmal caveolae but not as much as in the mature cell. They express SMMHC and, inconsistently, K14. This protein is consistently expressed in the mature cell. K14 is expressed by duct cells, and vimentin is expressed by both mesenchymal and epithelial cells.

After development, the acinar progenitor and the ductal progenitor appear to reside in the acinus/intercalated duct and the larger ducts, respectively, and to contribute to the tissue homeostasis. Under unusual conditions such as massive parenchymal destruction, the acinar progenitor contributes to the maintenance of the larger ducts that result in the occurrence of striated ducts with MECs. The acinar progenitor is the origin of salivary gland tumors containing MECs. MECs in salivary gland tumors are best identified by immunocytochemistry for -SMA. There are significant numbers of cells related to luminal tumor cells in the non-luminal tumor cells that have been believed to be neoplastic MECs.     

Different contents of glycosaminoglycans in a human neoplastic salivary duct cell line and its subclone with a myoepithelial phenotype

The glycosaminoglycans (GAG) biosynthesized by a neoplastic human salivary duct cell line, HSGc, and by its nontumorigenic subclone, HSGc-E1, having a myoepithelial-like phenotype, were examined by incorporation of [3H]-acetate into GAG. The rate of GAG radiolabeling in HSGc-E1 was significantly greater than that in HSGc. The radiolabeled GAG recovered from HSGc-E1 showed a distribution of 22-32% in the cells and 68-78% secreted into the medium, while the amounts of GAG in the cells and medium of HSGc were equal. Two-dimensional electrophoresis of GAG extracted from the cells demonstrated that HSGc-E1 contained a much greater amount of heparan sulfate (HS, 53.5% of total), while HSGc synthesized hyaluronic acid (HA, 17.5%), HS 38.8%, chondroitin sulfate (Ch-S, 27.6%) and dermatan sulfate (DS, 16.1%). Moreover, treatment of HSGc with sodium butyrate or dibutyryl cyclic AMP (each is a potent inducer of differentiation to myoepithelial-like cells) strongly enhanced GAG synthesis, while dexamethasone (an inducer of differentiation to a more functional duct epithelium) did not stimulate GAG synthesis. These findings suggest that biosynthetic changes in the GAG content of neoplastic salivary cells are associated with their myoepithelial differentiation.     

P63 is expressed in basal and myoepithelial cells of human normal and tumor salivary gland tissues.

p63 is essential for epithelial cell survival and may function as an oncogene. We examined by immunohistochemistry p63 expression in human normal and tumor salivary gland tissues. In normal salivary glands, p63 was expressed in the nuclei of myoepithelial and basal duct cells. Among 68 representative salivary gland tumors, 63 displayed p63 reactivity. In all tumor types differentiated towards luminal and myoepithelial lineages (pleomorphic adenomas, basal cell adenomas, adenoid cystic carcinomas, and epithelial-myoepithelial carcinomas), p63 was expressed in myoepithelial cells, whereas luminal cells were always negative. Similarly, in mucoepidermoid carcinomas, basal, intermediate, and squamous cells expressed p63, in contrast to luminal mucous cells. p63 reactivity was also restricted to basal cells in Warthin tumors and oncocytomas. Myoepitheliomas and myoepithelial carcinomas all expressed p63. The only five negative tumors were three of four acinar cell carcinomas and two of three adenocarcinomas. In conclusion, p63 is expressed in the nuclei of normal human salivary gland myoepithelial and basal duct cells. p63 expression is retained in the modified myoepithelial and basal cells of human salivary gland tumors, which suggests a role for p63 in oncogenesis of these complex tumors.     

Immunolocalization of centriole-associated striated rootlets in human submandibular gland cells with and without solitary cilia

Using an antibody specific to striated rootlets, we investigated the immuolocalization of striated rootlets in cells constituting human submandibular glands. Striated rootlets were positively stained in all cell types constituting acini, intercalated ducts, striated ducts, and interlobular ducts, but their shapes were different. The mean lengths of striated rootlets were 1.46 +/- 0.49, 3.15 +/- 1.35 and 3.99 +/- 1.02 microm in acinar secretory cells, myoepithelial cells, and columnar cells of the striated duct, respectively. The rootlets were the longest in columnar cells of the striated duct, in which paired centrioles were located in the apical cytoplasm away from nuclei. These findings suggest that striated rootlets play important roles in the positioning of centrioles in the cell. 2-8% of striated rootlets in myoepithelial cells were associated with solitary cilia, but they were not associated with solitary cilia in acinar cells and columnar cells of the striated duct. These observations suggest that striated rootlets may be associated with centrioles under normal physiological conditions, without formation of solitary cilia.     

Fine structural localization of acetylcholinesterase activity in rat submandibular gland

Using the indirect thiocholine method, the ultrastructural localization of acetylcholinesterase (AChE) activity in the normal rat submandibular gland was studied. Cytochemical demonstration of AChE is based on coupling the hydrolysis of acetylthiocholine iodide to the precipitation of heavy metal salts. AChE-associated reaction product was selectively revealed in the perinuclear space and in the endoplasmic reticulum of the intercalated duct cells, in some cells of granular convoluted tubules, and in the striated duct epithelium, as well as in the myoepithelial cells. Although AChE activity generally occurred inside the cells, electron-dense precipitates were shown in intercellular space and in the stroma of the gland. Fine localization of AChE activity was also found in nerve bundles, predominantly between axons and between axons and Schwann cell. Our observations indicate that AChE is synthesized in the epithelium of the ducts and in the myoepithelial cells of the salivary gland. It is not known yet whether this enzyme is released from the intracytoplasmic membrane system into the extracellular space and then transported to the regions of the gland innervation. Conceivably AChE synthesized in the submandibular gland cells could also be considered an inhibitory modulator of the regulatory functions of biologically active polypeptides.     

Immunocytochemical identification of myoepithelial cells in normal and neoplastic rat mammary glands with the lectins Griffonia simplicifolia-1 and pokeweed mitogen

Peroxidase-conjugated Griffonia simplicifolia-1 (GS-1) and pokeweed mitogen (PWM) histochemically stain only the myoepithelial cells and not the epithelial or fibroblastic cells of rat mammary glands preserved in methacarn or glutaraldehyde and embedded in paraffin. This pattern of staining occurs in other rat exocrine glands except the pancreas, but is the reverse of that seen in most lining epithelium. The histochemical binding of GS-1 and PWM to myoepithelial cells is inhibited specifically by D-galactose and by polymers of N-acetylglucosamine, respectively. GS-1 and its subcomponent, GS-1-B4, also bind to extracellular structures similar to those stained by anti-laminin serum. At the ultrastructural level, both conjugated GS-1 and PWM bind to the plasma membrane of the myoepithelial cells, as well as to the adjacent basement membrane. Non-metastasizing rat mammary tumors produced by dimethylbenz[a]anthracene, by derivative epithelial stem-cell lines, and by a transplantable tumor all contain more elongated myoepithelium-like cells as well as cuboidal epithelium-like cells; both cell types are neoplastic. The more elongated myoepithelium-like cells are stained by GS-1 and PWM, whereas the cuboidal epithelium-like cells are unstained. Moderately and strongly metastatic rat mammary tumors produced by epithelial cell lines and by transplantable tumors, respectively, contain no such neoplastic cells that bind either lectin. We suggest that the carbohydrate receptors for GS-1 and PWM are consistent markers for the presence of the myoepithelial cell in normal and tumorous rat mammary glands.     

Biological behavior of myoepithelial cells in the regeneration of rat atrophied sublingual glands following release from duct ligation

Summary The present study aimed to clarify how myoepithelial cells behave during regeneration of an atrophied sublingual gland by investigating cell proliferation and ultrastructure. Atrophy of rat sublingual glands was induced by unilateral ligation of the excretory duct near the hilum with metal clips, which were then removed after one week of ligation for regeneration. The sublingual glands 0–14 days after unligation were examined with single immunohistochemistry for actin as a marker of myoepithelial cells, double immunohistochemistry for actin and proliferating cell nuclear antigen (PCNA) as a marker of proliferating cells, and transmission electron microscopy (TEM). The single immunohistochemistry and TEM showed that myoepithelial cells surrounded residual ducts in the atrophied glands and immature and mature acini in the regenerating glands. Although PCNA-positive myoepithelial cells were identified during regeneration, PCNA labeling indices of myoepithelial cells were low at all time points except at day 7. Ultrastructurally, myoepithelial cells showing bizarre shaped structures in the atrophy changed with maturation of differentiating acinar cells and appeared normal in the regenerated glands. There was no differentiation of the remaining duct cells to myoepithelial cells. These observations suggest that proliferation of myoepithelial cells and differentiation to myoepithelial cells do not commonly participate in the regeneration of atrophied sublingual glands and that the bizarre shaped myoepithelial cells in the atrophied sublingual glands recover the original shapes with acinar cell regeneration.     

Aberrant p63 and WT-1 expression in myoepithelial cells of pregnancy-associated breast cancer: implications for tumor aggressiveness and invasiveness

Our recent studies revealed that focal alterations in breast myoepithelial cell layers significantly impact the biological presentation of associated epithelial cells. As pregnancy-associated breast cancer (PABC) has a significantly more aggressive clinical course and mortality rate than other forms of breast malignancies, our current study compared tumor suppressor expression in myoepithelial cells of PABC and non-PABC, to determine whether myoepithelial cells of PABC may have aberrant expression of tumor suppressors. Tissue sections from 20 cases of PABC and 20 cases of stage, grade, and age matched non-PABC were subjected to immunohistochemistry, and the expression of tumor suppressor maspin, p63, and Wilms' tumor 1 (WT-1) in calponin positive myoepithelial cells were statistically compared. The expression profiles of maspin, p63, and WT-1 in myoepithelial cells of all ducts encountered were similar between PABC and non-PABC. PABC, however, displayed several unique alterations in terminal duct and lobular units (TDLU), acini, and associated tumor tissues that were not seen in those of non-PABC, which included the absence of p63 and WT-1 expression in a vast majority of the myoepithelial cells, cytoplasmic localization of p63 in the entire epithelial cell population of some lobules, and substantially increasing WT-1 expression in vascular structures of the invasive cancer component. All or nearly all epithelial cells with aberrant p63 and WT-1 expression lacked the expression of estrogen receptor and progesterone receptor, whereas they had a substantially higher proliferation index than their counterparts with p63 and WT-1 expression. Hyperplastic cells with cytoplasmic p63 expression often adjacent to, and share a similar immunohistochemical and cytological profile with, invasive cancer cells. To our best knowledge, our main finings have not been previously reported. Our findings suggest that the functional status of myoepithelial cells may be significantly associated with tumor aggressiveness and invasiveness.     

Apoptosis and proliferation of myoepithelial cells in atrophic rat submandibular glands.

This study was designed to determine whether apoptosis and proliferation of myoepithelial cells occur in atrophic rat submandibular glands. The excretory duct of the right submandibular gland was doubly ligated with metal clips. The atrophic right submandibular glands removed after 1-28 days of duct ligation were investigated using immunohistochemical double staining for actin as a marker for myoepithelial cells and proliferating cell nuclear antigen (PCNA) as a marker for proliferating cells, double staining for actin immunohistochemistry, nick end-labeling (TUNEL) as a marker for apoptotic cells, and transmission electron microscopy (TEM). A few PCNA- and no TUNEL-positive myoepithelial cells were found in the control submandibular glands taken from animals with no operation. In the experimental glands, PCNA-positive myoepithelial cells were common 2 and 3 days after duct ligation and then decreased in number. TUNEL-positive myoepithelial cells appeared at 2 days and were observed most frequently at 5 days. Apoptotic myoepithelial cells were also identified by TEM. These observations suggest that both apoptosis and proliferation of myoepithelial cells occur, especially in the early phase of atrophy, in the rat submandibular gland.     

Hyperplasia of myoepithelial cells expressing calponin during atrophy of the rat parotid gland induced by duct ligation

The number and location of myoepithelial cells in the rat parotid gland submitted to surgical ligation of its main excretory duct were studied through immunohistochemical labelling for calponin. These cells were labelled by the streptavidin-biotin method using anti-calponin primary antibody, and their number was determined during each step of glandular atrophy, i.e., at time zero (control) and 1, 7, 15, 21, 30 and 60 days after ligation. Morphological analysis showed a gradual decrease and fibrosis of the glandular lobules accompanied by disappearance of the acini and the occurrence of duct-like structures. The expression of calponin was observed in all specimens analysed, being restricted to myoepithelial cells. Labelling revealed the distribution of myoepithelial cells around the acini and intercalated ducts in the control group and around duct-like structures later during the course of atrophy. Quantitative analysis demonstrated significant increase in the number of myoepithelial cells up to day 7 post-ligation, followed by gradual increases which, however, were not statistically significant. These results suggest that myoepithelial cells proliferate intensely up to day 7 post-ligation, an event that coincides with a higher rate of disappearance of acinar cells. After this period, the elevated number of cells observed at the end of the previous period is maintained.     

Epithelial-myoepithelial carcinoma of the parotid. A case of ductal-predominant presentation with cytologic, histologic and ultrastructural correlations

BACKGROUND: The cytologic features of the usual type of epithelial-myoepithelial carcinoma (EMC) of the parotid, with myoepithelial cell predominance, is well described in the cytology literature. In contrast, the cytologic features of ductal-predominant-type EMC has not yet been reported. CASE: An 82-year-old male presented with a 2.7-cm parotid mass of two years' duration. Fine needle aspiration smears stained with Diff-Quik showed cohesive tissue fragments outlined by metachromatic fibrils scattered in abundant, smooth, bluish background material. Ultrafast Papanicolaou stain revealed sharply outlined, large ductal cells with smooth, round to oval nuclei, prominent nucleoli and abundant vacuolated cytoplasm; the cells were arranged tridimensionally in occasional follicles that contained thick secretions. Neoplastic myoepithelial cells were occasionally seen at the periphery of tissue fragments, most commonly hidden underneath the neoplastic ductal epithelium at a slightly different focal plane; the cells had small, oval, dark nuclei and inconspicuous cell borders. The nuclear area and cell size of the neoplastic ductal cells was two and three times, respectively, that of neoplastic myoepithelial cells. CONCLUSION: EMC, depending on the ratio of ductal to myoepithelial cell components, has different cytologic presentations. This case illustrates the ductal-predominant presentation of EMC.     

The ultrastructure of the duct system in the rat extraorbital lacrimal gland

Summary The duct system of the rat exorbital lacrimal gland consists of intercalated ducts, interlobular ducts and excretory ducts. The morphological changes from one type of duct to the next are gradual. At the light microscopical level this consists of a change from a bilaminar epithelium in the intercalated ducts to an epithelium, consisting of approximately three layers — which may be pseudostratified — in the excretory ducts. The basal layer of the intercalated ducts consists of myoepithelial cells, whereas the inner epithelial cells may have both a secretory and an electrolyte transporting function. The interlobular duct epithelium contains many cells with deep infoldings of the basolateral plasma membranes and associated mitochondria, suggesting a similar function to the striated duct epithelium in salivary glands. Numerous basal cells in this epithelium have tentatively been interpreted as unusual myoepithelial cells. Nerve terminals have been observed in the ductal epithelium.This work was supported by the National Health and Medical Research Council of Australia. — We wish to thank Mrs. Eva Vasak for her expert technical assistance.     

Cytogenesis of murine mammary tumors in BALB/cfC3H and BALB/cfRIII strains

Biological and morphological differences in the mammary tumors of BALB/cfC3H and BALB/cfRIII mice are due to differences in the causative viruses. The C3H and RIII variants of the murine mammary tumor virus (MuMTV) might give origin to different mammary tumors by transforming different types of cell, i.e. epithelial or myoepithelial cells. The nature (epithelial or myoepithelial) of the neoplastic cells has been investigated by demonstrating their plasma membrane ATPase activities. We found that in normal murine mammary gland both epithelium and myoepithelium have Mg++ dependent ATPase activity, while the myoepithelium shows in addition an Na+K+ dependent ATPase activity. It is suggested that the results obtained exclude the participation of myoepithelium to the neoplastic growth and we ascribe the differences in mammary tumors of the two strains of mice to differences in the mechanisms of action of the virus variants.