共查询到20条相似文献,搜索用时 62 毫秒
1.
Joseph A. DePasquale 《Histochemistry and cell biology》1998,110(5):485-494
Interference reflection microscopy (IRM) was used to evaluate the status of cell matrix adhesions in the MCF-7 human mammary
carcinoma cell line. Focal contacts were concentrated at the periphery of individual cells or small cell clusters. Close contact
was detected as a band at cell peripheries and as localized patches throughout the ventral face of cells. The MCF-7 cells
also exhibited a distinctive reflection pattern of an intensity midway between that of either focal or close contact. This
novel reflection pattern was located primarily at the periphery of cells and often obscured visualization of focal contacts
in live cells. A similar distinctive pattern was absent from the normal tissue-derived MCF-10A mammary epithelial cell line.
Immunofluorescence staining using an antiserum that cross-reacts with both αvβ3 and αvβ5 integrins revealed a distribution of the vitronectin receptor similar to that of the novel adhesion pattern as well as to
that of focal contacts. In addition, IRM demonstrated the presence of ”tracks” associated with cells, which were also stained
with the vitronectin receptor antiserum. The tracks are apparently residual material left behind as a result of cell migration.
When MCF-7 cells were cultured in the absence of estradiol, the tracks were greatly diminished when visualized with either
IRM or staining for the vitronectin receptor. In contrast, the addition of 17-β-estradiol to the medium resulted in an increased
presence of the tracks as well as the development of extensive close contacts throughout the ventral surface of cells and
cell clusters. Cells treated with the estrogen antagonist ICI 182,720 in the presence of estradiol had few associated tracks,
indicating that the process leading to the formation of these structures is dependent on an estrogen receptor-activated pathway.
However, the antagonist did not prevent the estradiol-induced formation of extensive close contacts. The extensive close contact
as well as the increase in trailing material suggests that estradiol may promote breast tumor cell motility. However, this
migratory activity may be mediated by both estrogen receptor-dependent and -independent pathways.
Accepted: 29 May 1998 相似文献
2.
In the present work, potential protective effects of quercitrin (a phytoestrogen) on Aβ-induced neurotoxicity in cultured
rat hippocampal neurons were investigated in comparison with 17β-estradiol. Cell viability, oxidative status, and antioxidative
potentials were used as comparative parameters. Co-exposure of cultured neurons to Aβ25–35 with either quercitrin or 17β-estradiol (50–100 μM) for 72 h attenuated Aβ25–35-induced neurotoxicity and lipid peroxidation, but not Aβ25–35-induced ROS accumulation. However, only 17β-estradiol counteracted a reduction in glutathione content and only quercitrin
counteracted a reduction in glutathione peroxidase activity. Both compounds displayed no effects on superoxide dismutase activity.
A specific estrogen receptor antagonist, ICI 182780, did not abolish neuroprotective effects of quercitrin and 17β-estradiol.
These findings suggested that quercitrin and 17β-estradiol attenuated Aβ25–35-induced neurotoxicity in a comparable manner. Underlying neuroprotective mechanisms of both compounds were probably not related
to estrogen receptor-mediated genomic mechanisms but might involve with their antioxidant and free radical scavenging properties. 相似文献
3.
Marco Felkl Kazmar Tomas Matej Smid Julian Mattes Reinhard Windoffer Rudolf E. Leube 《PloS one》2012,7(9)
Altered cell motility is considered to be a key factor in determining tumor invasion and metastasis. Epidermal growth factor (EGF) signaling has been implicated in this process by affecting cytoskeletal organization and dynamics in multiple ways. To sort the temporal and spatial regulation of EGF-dependent cytoskeletal re-organization in relation to a cell’s motile behavior time-lapse microscopy was performed on EGF-responsive gastric carcinoma-derived MKN1 cells co-expressing different fluorescently labeled cytoskeletal filaments and focal adhesion components in various combinations. The experiments showed that EGF almost instantaneously induces a considerable increase in membrane ruffling and lamellipodial activity that can be inhibited by Cetuximab EGF receptor antibodies and is not elicited in non-responsive gastric carcinoma Hs746T cells. The transient cell extensions are rich in actin but lack microtubules and keratin intermediate filaments. We show that this EGF-induced increase in membrane motility can be measured by a simple image processing routine. Microtubule plus-ends subsequently invade growing cell extensions, which start to accumulate focal complexes at the lamellipodium-lamellum junction. Such paxillin-positive complexes mature into focal adhesions by tyrosine phosphorylation and recruitment of zyxin. These adhesions then serve as nucleation sites for keratin filaments which are used to enlarge the neighboring peripheral keratin network. Focal adhesions are either disassembled or give rise to stable zyxin-rich fibrillar adhesions which disassemble in the presence of EGF to support formation of new focal adhesion sites in the cell periphery. Taken together the results serve as a basis for modeling the early cytoskeletal EGF response as a tightly coordinated and step-wise process which is relevant for the prediction of the effectiveness of anti-EGF receptor-based tumor therapy. 相似文献
4.
Schwab W Kasper M Gavlik JM Schulze E Funk RH Shakibaei M 《Histochemistry and cell biology》2000,113(3):221-225
Interactions between the extracellular matrix (ECM) and chondrocytes are of great importance for structure and function of
cartilage. The present study was undertaken to answer the question whether caveolins take part in integrin-mediated cell–ECM
interactions in the human cartilage. In samples of human knee joint cartilage, we detected the caveolin subtypes -1, -2, and
-3 by immunohistochemical methods. Double-label experiments revealed a colocalization of caveolin with β1-integrin. Results
of immunoprecipitation and immunoblotting assays show that β1-integrins associate with all three caveolin subtypes in human
chondrocytes and indicate that they are part of the same complexes. Furthermore, immunoelectron microscopy shows the localization
of β1-integrin in caveolae-like structures of the cell membrane. The data stimulate further investigations on the role of
the caveolin–integrin complex for integrin-mediated signaling pathways in chondrocytes.
Accepted: 17 December 1999 相似文献
5.
Localization and activity of calmodulin is involved in cell–cell adhesion of tumor cells and endothelial cells in response to hypoxic stress 总被引:2,自引:0,他引:2
Shen WG Peng WX Shao Y Xu JF Dai G Zhang Y Pan FY Li CJ 《Cell biology and toxicology》2007,23(5):323-335
Adhesion of tumor cells to endothelial cells is known to be involved in the hematogenous metastasis of cancer, which is regulated
by hypoxia. Hypoxia is able to induce a significant increase in free intracellular Ca2+ levels in both tumor cells and endothelial cells. Here, we investigate the regulatory effects of calmodulin (CaM), an intracellular
calcium mediator, on tumor cell–endothelial cell adhesion under hypoxic conditions. Hypoxia facilitates HeLa cell–ECV304 endothelial
cell adhesion, and results in actin cytoskeleton rearrangement in both endothelial cells and tumor cells. Suppression of CaM
activation by CaM inhibitor W-7 disrupts actin cytoskeleton organization and CaM distribution in the cell–cell contact region,
and thus inhibits cell–cell adhesion. CaM inhibitor also downregulates hypoxia-induced HIF-1-dependent gene expression. These
results suggest that the Ca2+-CaM signaling pathway might be involved in tumor cell-endothelial cell adhesion, and that co-localization of CaM and actin
at cell–cell contact regions might be essential for this process under hypoxic stress.
W.-G. Shen and W.-X. Peng Contributed to this paper equally 相似文献
6.
Estrogen-like properties of brominated analogs of bisphenol A in the MCF-7 human breast cancer cell line 总被引:1,自引:0,他引:1
M. Samuelsen C. Olsen J.A. Holme E. Meussen-Elholm A. Bergmann J.K. Hongslo 《Cell biology and toxicology》2001,17(3):139-151
Tetrabromobisphenol A (TeBBPA) is a four-meta-brominated variant of bisphenol A (BPA) and is one of the most commonly used brominated flame retardants worldwide. We compared
the estrogenic potency of TeBBPA, BPA and the brominated analogs mono- (MBBPA), di- (DBBPA), and tribromobisphenol A (TrBBPA)
in the estrogen-dependent human breast cancer cell line MCF-7. All of the compounds competed with 17β-estradiol for binding
to the estrogen receptor, although the affinity of the test chemicals to the estrogen receptor was much lower than that of
17β-estradiol. TrBBPA and TeBBPA showed a considerably lower access to the estrogen receptors within intact MCF-7 cells incubated
in 100% serum compared to incubation in serum-free medium, indicating a strong binding to serum proteins. BPA, MBBPA, and
DBBPA showed only a slightly reduced access to the receptors. All of the test compounds induced proliferation in MCF-7 cells,
the potential decreasing with increasing number of bromo-substitutions. TeBBPA did not induce maximal cell growth, indicating
cytotoxic effects at high concentrations. BPA and the brominated analogs, except TeBBPA, induced progesterone receptor and
pS2 to the same extent as 17β-estradiol, although at much higher concentrations. Our studies demonstrate that compared to
17β-estradiol, BPA and the brominated analogs have much lower estrogenic potencies for all of the endpoints tested, TeBBPA
being the least estrogenic compound.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
7.
Bai W Oliveros-Saunders B Wang Q Acevedo-Duncan ME Nicosia SV 《In vitro cellular & developmental biology. Animal》2000,36(10):657-666
Summary Ovarian cancer is the leading cause of gynecological cancer mortality, and 85–90% of this malignancy originates from the ovarian
surface epithelium (OSE). The etiology of ovarian epithelial cancer is unknown but a role for estrogens has been suspected.
However, the effect of estrogens on OSE cell proliferation remains to be determined. Using the rabbit model, our studies have
demonstrated that 17β-estradiol stimulates OSE cell proliferation and the formation of a papillary ovarian surface morphology
similar to that seen in human ovarian serous neoplasms of low malignant potential. Immunohistochemical staining of ovarian
tissue sections with an antibody to the estrogen receptor α demonstrates its expression in both OSE cells and stromal interstitial
cells. In primary ovarian cell cultures, the proliferative response of the epithelial cells to 17β-estradiol depends on the
expression of the estrogen receptor α in the epithelial cells. However, when the epithelial cells are grown together with
ovarian stromal cells, their proliferative response to this hormone is greatly enhanced, suggesting the involvement of stromal-epithelial
interactions. These studies suggest a role for estrogens and the estrogen receptor α in OSE growth. 相似文献
8.
9.
Pierre-Olivier Strale Laurence Duchesne Grégoire Peyret Lorraine Montel Thao Nguyen Evelyn Png Robert Tampé Sergey Troyanovsky Sylvie Hénon Benoit Ladoux René-Marc Mège 《The Journal of cell biology》2015,210(2):333-346
Oligomerization of cadherins could provide the stability to ensure tissue cohesion. Cadherins mediate cell–cell adhesion by forming trans-interactions. They form cis-interactions whose role could be essential to stabilize intercellular junctions by shifting cadherin clusters from a fluid to an ordered phase. However, no evidence has been provided so far for cadherin oligomerization in cellulo and for its impact on cell–cell contact stability. Visualizing single cadherins within cell membrane at a nanometric resolution, we show that E-cadherins arrange in ordered clusters, providing the first demonstration of the existence of oligomeric cadherins at cell–cell contacts. Studying the consequences of the disruption of the cis-interface, we show that it is not essential for adherens junction formation. Its disruption, however, increased the mobility of junctional E-cadherin. This destabilization strongly affected E-cadherin anchoring to actin and cell–cell rearrangement during collective cell migration, indicating that the formation of oligomeric clusters controls the anchoring of cadherin to actin and cell–cell contact fluidity. 相似文献
10.
Paszek MJ DuFort CC Rubashkin MG Davidson MW Thorn KS Liphardt JT Weaver VM 《Nature methods》2012,9(8):825-827
Emerging questions in cell biology necessitate nanoscale imaging in live cells. Here we present scanning angle interference microscopy, which is capable of localizing fluorescent objects with nanoscale precision along the optical axis in motile cellular structures. We use this approach to resolve nanotopographical features of the cell membrane and cytoskeleton as well as the temporal evolution, three-dimensional architecture and nanoscale dynamics of focal adhesion complexes. 相似文献
11.
The mammary gland undergoes hormonally controlled cycles of pubertal maturation, pregnancy, lactation, and involution, and
these processes rely on complex signaling mechanisms, many of which are controlled by cell–cell and cell–matrix adhesion.
The adhesion of epithelial cells to the extracellular matrix initiates signaling mechanisms that have an impact on cell proliferation,
survival, and differentiation throughout lactation. The control of integrin expression on the mammary epithelial cells, the
composition of the extracellular matrix and the presence of secreted matricellular proteins all contribute to essential adhesion
signaling during lactogenesis. In vitro and in vivo studies, including the results from genetically engineered mice, have
shed light on the regulation of these processes at the cell and tissue level and have led to increased understanding of the
essential signaling components that are regulated in temporal and cell specific manner during lactogenesis. Recent studies
suggest that a secreted matricellular protein, CTGF/CCN2, may play a role in lactogenic differentiation through binding to
β1 integrin complexes, enhancing the production of extracellular matrix components and contributions to cell adhesion signaling. 相似文献
12.
Nuclear magnetic resonance (NMR) spectroscopy is a useful biophysical technique to study the ligand–protein interaction. In
this report, we have used bacterially produced ERβ and its domains for studying the functional analysis of ligand–protein
interaction. Briefly, ERβ and its transactivation domain (TAD) and ligand binding domain (LBD) were subcloned and overexpressed
using a prokaryotic expression system. The recombinant proteins were purified using Ni+2-IDA affinity chromatography and analyzed by NMR. Purified ERβ and TAD show similar conformation in the absence or presence
of 17β-estradiol. However, LBD shows altered conformation in the presence of 17β-estradiol. These findings suggest that ERβ
produced in bacteria exhibits a conformation such that its LBD remains masked and consequently it binds less to 17β-estradiol.
Such study may help to develop the therapeutic approaches for controlling the estradiol-mediated gene expression in hormone
dependent diseases. 相似文献
13.
Sánchez JC López-Zapata DF Francis L De Los Reyes L 《Cellular and molecular neurobiology》2011,31(4):619-627
The Na+/Ca2+ exchanger (NCX) is an important bidirectional transporter of calcium in neurons and has been shown to be involved in neuroprotection.
Calcium can activate a number of cascades that can result in apoptosis and cell death, and NCX is a key factor in regulating
the cytoplasmic concentration of this ion. 17-β-estradiol and insulin-like growth factor 1 (IGF-1) are known neuroprotective
hormones with interacting mechanisms and effects on intracellular calcium; however, their relationship with the NCX has not
been explored. In this article, the effects of these two hormones on neuronal NCX were tested using the whole-cell patch clamp
technique on rat primary culture neurons. Both 17-β-estradiol and IGF-1 produced an increase in the NCX-mediated inward current
and a decrease in the NCX-mediated outward current. However, the IGF-1 effect was lower than that of 17-β-estradiol, and the
effect of both agents together was greater than the sum of each agent alone. Neither of the agents affected the pattern of
regulation by extracellular or intrapipette calcium. Inhibitors of the IGF-1 and 17-β-estradiol receptors and inhibitors of
the main signaling pathways failed to change the observed effects, indicating that these actions were not mediated by the
classical receptors of these hormones. These effects on the NCX could be a mechanism explaining the neuroprotective actions
of 17-β-estradiol and IGF-1, and these findings could help researchers to understand the role of the NCX in neuroprotection. 相似文献
14.
In epithelial MDCK cells, the Na,K-ATPase is co-localized with adherens junctions in all stages of monolayer formation starting
from initiation of cell–cell contact. The Na,K-ATPase and adherens junction proteins stay partially co-localized even after
internalization due to disruption of intercellular contacts by Ca2+ deprivation. Similar to adherens junction proteins, the Na,K-ATPase is resistant to extraction with non-ionic detergent,
suggesting pump association with the cytoskeleton. In contrast, the heterodimer formed by expressed unglycosylated Na,K-ATPase
β1 subunit and the endogenous α1 subunit is easily dissociated from the adherens junctions and cytoskeleton by detergent extraction. The MDCK cells in which
half of the endogenous β1 subunits in the lateral membrane are substituted by unglycosylated β1 subunits display a slower rate of cell-to-cell contact formation and decreased ability to both spread over the surface and
migrate. The lack of N-glycans in the Na,K-ATPase β1 subunit results in an impairment of mature cell–cell junctions as detected by an increase in the paracellular permeability
of the MDCK cell monolayers and by a decrease in resistance of adherens junction proteins to extraction by a non-ionic detergent.
Therefore the N-glycans of the Na,K-ATPase β1 subunit are important for retention of the pump at the sites of cell–cell contact. Moreover, they are important for the integrity
and stability of cell–cell junctions in mature epithelia. In addition, N-glycans contribute to the formation of cell–cell
contacts between surface-attached dispersed cells by mediating lamellipodia formation and stabilizing the newly formed adherens
junctions. 相似文献
15.
Melissa Morley Claire Jones Mandeep Sidhu Vishal Gupta Suzanne M. Bernier Walter J. Rushlow Daniel J. Belliveau 《Cell and tissue research》2010,340(2):229-242
Gap junction intercellular communication and cell–cell adhesion are essential for maintaining a normal cellular phenotype,
including the control of growth and proliferation. Loss of either cell–cell adhesion or communication is common in cancers,
while restoration of function is associated with tumor suppression. Protein kinase C (PKC) isozymes regulate a broad spectrum
of cellular functions including growth and proliferation, and their overexpression has been correlated with carcinogenesis.
Consequently, PKC inhibitors are currently undergoing clinical trials as an anti-cancer agents although the precise cellular
alterations induced by PKC inhibitors remain to be elucidated. In the current study, the effects of PKC inhibitors on cell
interactions were investigated using human neuroblastoma (IMR32, SKNMC, and SHSY-5Y) cell lines. An analysis of intercellular
communication revealed an increase in gap junctional coupling with PKC inhibition. The observed increase in coupling was not
associated with a change in Connexin43 distribution or an alteration of phosphorylation status of the protein. There was also
an increase in cell–cell adhesion with PKC inhibitor treatment as indicated by a cell aggregation assay. Therefore, the growth
suppressive abilities of PKC inhibition on tumors may be due to the cancer suppressive effects of increased gap junction intercellular
communication and cell–cell adhesion. 相似文献
16.
Sanchez AM Flamini MI Baldacci C Goglia L Genazzani AR Simoncini T 《Molecular endocrinology (Baltimore, Md.)》2010,24(11):2114-2125
The ability of cancer cells to move and invade the surrounding environment is the basis of local and distant metastasis. Cancer cell movement requires dynamic remodeling of the cytoskeleton and cell membrane and is controlled by multiprotein complexes including focal adhesion kinase (FAK) or the Neural Wiskott-Aldrich Syndrome Protein (N-WASP). We show that 17β-estradiol induces phosphorylation of FAK and its translocation toward membrane sites where focal adhesion complexes are assembled. This process is triggered via a Gα/Gβ protein-dependent, rapid extranuclear signaling of estrogen receptor α interacts in a multiprotein complex with c-Src, phosphatidylinositol 3-OH kinase, and FAK. Within this complex FAK autophosphorylation ensues, and activated FAK recruits the small GTPase cdc42, which, in turn, triggers N-WASP phosphorylation. This results in the translocation of Arp2/3 complexes at sites where membrane structures related to cell movement are formed. Recruitment of FAK and N-WASP is necessary for cell migration and invasion induced by 17β-estradiol in breast cancer cells. Our findings identify an original mechanism through which estrogen promotes breast cancer cell motility and invasion. This information helps to understand the effects of estrogen on breast cancer metastasis and may provide new targets for therapeutic interventions. 相似文献
17.
Summary. Mammalian testis contains D-aspartic acid (D-Asp), which enhances testosterone production. D-Asp, on other hand, also stimulates
17β-estradiol synthesis in the ovary of some lower vertebrates. We studied boar testis in order to determine if D-Asp intervenes
in 17β-estradiol synthesis in the testis of those mammals which produce significant amounts of estrogens as well as testosterone.
The boar testis contains D-Asp (40 ± 3.6 nmol/g tissue) which, according to immunohistological techniques, is localized mainly
in Leydig cells, and, to a lesser extent, in sustentacular (Sertoli), peritubular and some germ cells. The enzyme P450aromatase
is present in Leydig cells and few germ cells. In vitro experiments showed that the addition of D-Asp to testicular tissue
extracts induced a significant increase of aromatase activity, as evaluated by testosterone conversion into 17β-estradiol.
The enzyme’s Km was not affected by D-Asp (about 25 nM in both control and D-Asp added tests). On the basis of these results we suggest that,
as in the ovary, D-Asp is involved in the local control of aromatase activity of boar testis and, therefore, it intervenes
in the 17β-estradiol production. In the testis, the D-Asp targets are presumably the Leydig cells, which having also a nuclear
estrogen receptor are, in turn, one of the putative targets of the 17β-estradiol that they produce (autocrine effect). 相似文献
18.
Abeer M. Al-Ghananeem Ashraf A. Traboulsi Lewis W. Dittert Anwar A. Hussain 《AAPS PharmSciTech》2002,3(1):40-47
The utility of the nasal route for the systemic delivery of 17β-estradiol was studied using watersoluble prodrugs of 17β-estradiol.
This delivery method was examined to determine if it will result in preferential delivery to the brain. Several alkyl prodrugs
of 17β-estradiol were prepared and their physicochemical properties were determined. In vitro hydrolysis rate constants in
buffer, rat plasma, and rat brain homogenate were determined by high-performance liquid chromatography. In vivo nasal experiments
were carried out on rats. Levels of 17β-estradiol in plasma and cerebral spinal fluid (CSF) were determined with radioimunoassay
using a gamma counter. The study revealed that the aqueous solubilities of the prodrugs were several orders of magnitude greater
than 17β-estradiol with relatively fast in vitro conversion in rat plasma. Absorption was fast following nasal delivery of
the prodrugs with high bioavailability. CSF 17β-estradiol concentration was higher following nasal delivery of the prodrugs
compared to an equivalent intravenous dose. It was determined that water-soluble prodrugs of 17β-estradiol can be administered
nasally. These prodrugs are capable of producing high levels of estradiol in the CSF and as a result may have a significant
value in the treatment of Alzheimer's disease.
Published: March 25, 2002. 相似文献
19.
Protein tyrosine phosphatases (PTPs) regulate various physiological events in animal cells. They comprise a diverse family
which are classified into two categories, receptor type and nonreceptor type. From the domain organization and phylogenetic
tree, we have classified known PTPs into 17 subtypes (9 receptor-type and 8 nonreceptor-type PTPs) which are characterized
by different organization of functional domain and independent cluster in tree. The receptor type PTPs are thought to be implicated
in cell–cell adhesion by association of cell adhesion molecules. Since sponges are the most primitive multicellular animals
and are thought to be lacking cell cohesiveness and coordination typical of eumetazoans, cloning and sequencing of PTP cDNAs
of Ephydatia fluviatilis (freshwater sponge) have been conducted by RT-PCR to determine whether or not sponges have PTP genes in their genomes. We
have isolated nine PTPs, of which five are possibly receptor type. A phylogenetic tree including the sponge PTPs revealed
that most of the gene duplications that gave rise to the 17 subtypes had been completed in the very early evolution of animals
before the parazoan–eumetazoan split, the earliest branching among extant animal phyla. The family tree also revealed the
rapid evolutionary rate of PTP subtypes in the early stage of animal evolution.
Received: 22 October 1998 / Accepted: 27 November 1998 相似文献
20.
Kathy N. Astrahantseff John E. Morris 《In vitro cellular & developmental biology. Animal》1994,30(11):769-776
Summary There is indirect evidence that the in vivo proliferative response of rodent uterine epithelium to estrogen requires interaction
with the underlying stroma in pre- and post-pubescent animals. To examine this potential requirement directly, the proliferative
response of epithelium to 17β-estradiol in the presence or absence of stroma was measured in vitro. Uterine epithelial and stromal cells were isolated
separately from immature or adult mice, and were maintained as monocultures or cocultures in defined, serum-free medium with
or without 8 × 10−9
M 17β-estradiol. Incorporation of bromodeoxyuridine into the DNA was determined by immunolabeling to assay proliferation in individual
cells. Cell morphology and immunolabeling of cytokeratin were used to distinguish epithelial from stromal cells. Treatment
of cocultures with 17β-estradiol for 24 h increased the proliferation of epithelial cells relative to controls approximately threefold, whereas,
in monocultures of epithelial or stromal cells 17β-estradiol decreased the number of bromodeoxyuridine-incorporating cells by approximately half. Furthermore, cell contact
between epithelial and stromal cells was important for the effects of 17β-estradiol on cells in cocultures. Approximately three quarters of the 17β-estradiol-induced proliferation of epithelial cells in cocultures was produced by epithelial cells within colonies that were
also contacting stromal cells. These results are consistent with the hypothesis that stromal cells mediate the estrogenic
proliferative response, and provide evidence that this mediation involves cell contact or stroma-mediated changes in the microenvironment
immediately around the epithelial cell. 相似文献