共查询到20条相似文献,搜索用时 93 毫秒
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Romieu-Mourez R Kim DW Shin SM Demicco EG Landesman-Bollag E Seldin DC Cardiff RD Sonenshein GE 《Molecular and cellular biology》2003,23(16):5738-5754
Amplification, overexpression, or rearrangement of the c-rel gene, encoding the c-Rel NF-kappaB subunit, has been reported in solid and hematopoietic malignancies. For example, many primary human breast cancer tissue samples express high levels of nuclear c-Rel. While the Rev-T oncogene v-rel causes tumors in birds, the ability of c-Rel to transform in vivo has not been demonstrated. To directly test the role of c-Rel in breast tumorigenesis, mice were generated in which overexpression of mouse c-rel cDNA was driven by the hormone-responsive mouse mammary tumor virus long terminal repeat (MMTV-LTR) promoter, and four founder lines identified. In the first cycle of pregnancy, the expression of transgenic c-rel mRNA was observed, and levels of c-Rel protein were increased in the mammary gland. Importantly, 31.6% of mice developed one or more mammary tumors at an average age of 19.9 months. Mammary tumors were of diverse histology and expressed increased levels of nuclear NF-kappaB. Analysis of the composition of NF-kappaB complexes in the tumors revealed aberrant nuclear expression of multiple subunits, including c-Rel, p50, p52, RelA, RelB, and the Bcl-3 protein, as observed previously in human primary breast cancers. Expression of the cancer-related NF-kappaB target genes cyclin D1, c-myc, and bcl-xl was significantly increased in grossly normal transgenic mammary glands starting the first cycle of pregnancy and increased further in mammary carcinomas compared to mammary glands from wild-type mice or virgin transgenic mice. In transient transfection analysis in untransformed breast epithelial cells, c-Rel-p52 or -p50 heterodimers either potently or modestly induced cyclin D1 promoter activity, respectively. Lastly, stable overexpression of c-Rel resulted in increased cyclin D1 and NF-kappaB p52 and p50 subunit protein levels. These results indicate for the first time that dysregulated expression of c-Rel, as observed in breast cancers, is capable of contributing to mammary tumorigenesis. 相似文献
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John C. Angello Howard L. Hosick 《Biochemical and biophysical research communications》1982,107(3):1130-1137
Multicellular aggregates of tumorigenic mouse mammary epithelial cells contain a hyaluronate-rich matrix, both at the aggregate periphery and within the growing spheroid. It is proposed that the establishment of a hyaluronaterich matrix is essential to spheroid growth in vitro, and that the spheroid is a good model system for analysis of this aspect of early tumor development. 相似文献
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Genetics of mouse mammary tumor virus-induced mammary tumors: linkage of tumor induction to the gag gene 下载免费PDF全文
Retroviruses are believed to induce tumors by acting as insertional mutagens that activate expression of cellular protooncogenes. Indeed, almost 90% of mouse mammary tumor virus (MMTV)-induced mammary tumors in C3H/He mice show upregulation of Int protooncogenes. We have analyzed three different MMTV variants [MMTV(C3H), MMTV(HeJ), and a genetically engineered MMTV hybrid provirus (HP)] for tumorigenicity in mice from two distinct genetic backgrounds. All three viruses were tumor causing in BALB/cJ mice. However, only MMTV(C3H), but not MMTV(HeJ) or HP, induced mammary tumors in C3H/He mice. All of the viruses were infectious on either background and up-regulated expression of Int genes in tumors they induced. Like HP, MMTV(HeJ) was found to be a genetic recombinant between endogenous Mtv1 provirus and exogenous MMTV(C3H). Sequence comparison of MMTV variants linked the tumorigenicity of MMTV(C3H) to the gag region of the retrovirus. 相似文献
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Amiano N Reiteri RM Costa MJ Tateosian N Chuluyan HE 《Cancer immunology, immunotherapy : CII》2011,60(6):895-900
We have demonstrated previously that the inoculation of murine mammary tumor cells genetically modified to express high levels
of secretory leukocyte protease inhibitor (2C1) do not develop tumors in immunocompetent mice and these cells are more prone
to apoptosis than control cells. The aim of the present study was to evaluate the role of the adaptive immune response in
the lack of tumor growth of 2C1 cells and the possibility of using these cells for immunotherapy. The s.c. administration
of mock transfected F3II cells induces tumor in BALB/c and Nude mice. However, the inoculation of 2C1 cells develops tumor
in Nude but not in BALB/c mice. The inoculation of mock transfected F3II cells to 2C1 immunized BALB/c mice by repeated administration
of 2C1 cells (once a week for 3 weeks) developed significantly smaller tumors than those observed in non-immunized mice. Remarkably,
survival of tumor-bearing immunized mice was higher than non-immunized animals. Herein, we demonstrate that an immunotherapy
with SLPI over-expressing non-irradiated tumor cells which do not develop tumor in immunocompetent mice, partially restrain
the tumor growth induced by F3II cells and increase the survival of the mice. 相似文献
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Richard F. Bauer Larry O. Arthur Donald L. Fine 《In vitro cellular & developmental biology. Plant》1976,12(8):558-563
Summary Five different mouse mammary tumor cell lines were propagated in a serum free medium. Evaluation of growth characteristics,
including logarithmic growth, cell population increase, protein production and days to confluency, showed serum-free medium
comparable to serum-containing medium. Mouse mammary tumor virus expression and production, in C3H and GR tumor cell lines, as determined by virus particle counting and RNA dependent DNA polymerase assays, subsequent to
dexamethasone stimulation revealed equivalent to higher levels of virus in serum-free medium as compared to serum-containing
medium. 相似文献
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Fred R. Miller 《Cancer immunology, immunotherapy : CII》1985,20(3):219-222
Summary The mouse mammary fatpad is immunologically privileged relative to the subcutis for the transplantation of nonmalignant tissues. Mouse mammary tumors, however, induce tumor-specific immunity in the mammary fatpad. Immunizing tumor cells were injected into the fatpad or subcutis at several time periods before challenge tumor cells were injected into the subcutis on the contralateral side and the time of onset of concomitant immunity was determined. Mice immunized by transplantion of tumor cells into the subcutis became resistant to challenge tumor transplants before mice immunized with tumor cells transplanted into the fatpad. By utilizing a metastatic tumor line which is resistant to thioguanine and ouabain, it was directly demonstrated that tumor cells from a s.c. implant reached the regional inguinal lymph node before tumor cells from a mammary fatpad tumor implant. 相似文献
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Cryoelectron microscopy of Mouse mammary tumor virus, a Betaretrovirus, provided information about glycoprotein structure and core formation. The virions showed the broad range of diameters typical of retroviruses. Betaretroviruses assemble cytoplasmically, so the broad size range cannot reflect the use of the plasma membrane as a platform for assembly. 相似文献
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M Sluyser B Moncharmont G Ramp C C de Goeij S G Evers 《Journal of steroid biochemistry》1987,27(1-3):209-214
In view of reports that human breast cancer cells secrete growth factors that can replace estradiol in sustaining tumor growth [1], we have investigated whether hormone independent (HI) GR mouse mammary tumors can sustain growth of estrogen-depleted hormone dependent (HD) tumors. HD GR mammary tumor TSl 106 was grafted subcutaneously in the right flank of estrone plus progesterone treated castrated (020 X GR)F1 mice. After 2 weeks the estrone treatment was stopped and the mice received 50, 100 or 150 mg HI GR mammary tumor TSl 104 in the left flank. However, the regression of the HD tumor due to estrone depletion was not prevented or retarded by the HI grafts. In other experiments we investigated integrations of mouse mammary tumor virus (MMTV) proviral DNA in the DNA of GR mammary tumors. We could demonstrate the presence of two cell populations in tumor TSl 96, both HD but differing in MMTV DNA integration events. Our data indicate that exogenous integrations of MMTV proviruses can take place in mouse mammary tumor DNA without loss of hormone dependency of the tumors. Like in GR/Mtv-2+ mice, mammary tumor transplants differing in MMTV proviral integrations are also observed in 020/Mtv-2+ mice. 相似文献
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This study describes a differential frequency of spontaneous fusion between metastatic and nonmetastatic subpopulations derived from a single mouse mammary tumor. Subpopulations 66, 66c14 (a variant of 66 which is resistant to both thioguanine and ouabain), 410.4, and 44FTO (a thioguanine-resistant, ouabain-resistant derivative of 410.4) spontaneously metastasize from subcutaneous and mammary fatpad sites. Subpopulations 168, 168FARO (a diaminopurine-resistant, ouabain-resistant derivative of 168), 67, 68H, and 410 do not. The ability of these subpopulation lines to fuse spontaneously in vitro was determined after coculturing a drug-resistant line with a wild-type line in nonselective media. After 16-20 h of coculture, cells were plated in the appropriate media to select for fusion products--either HAT (hypoxanthine, aminopterin, thymidine) plus ouabain or AA (alanosine, adenine) plus ouabain--to determine the number of colony-forming cells (fusion products) present per 10(4) cells plated. When both subpopulations of the pair in the fusion mixture were metastatic, a significantly greater number of fusion products was recovered than if one or both of the subpopulations in the fusion mixture was nonmetastatic, with one exception: line 410 readily fused with both 66c14 and 44FTO. Subline 410 was highly metastatic when originally isolated but lost its metastatic competence after a brief time in tissue culture. 相似文献
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Expression of secreted frizzled-related protein 2 in a primary canine mammary tumor cell line: a candidate tumor marker for mammary tumor cells 总被引:2,自引:0,他引:2
Lee JL Chang CJ Chueh LL Lin CT 《In vitro cellular & developmental biology. Animal》2003,39(5-6):221-227
Canine mammary tumors (CMTs) have been proposed to be a good animal model for human breast cancer. To provide a basis for the tumorigenic study of CMTs, cell lines were established using a modified cell culture technique. The epithelial morphology and immunostaining with cytokeratin 18 confirmed the epithelial origin of the cells. In an investigation of possible mammary tumorigenesis-related factors, the expression of Wnt signaling-related proteins was detected in cell lines. Secreted frizzled-related protein 2 (SFRP2) was abundantly expressed in CMT cells but not in normal canine mammary gland (MG) cells. Secreted frizzled-related protein 2 was secreted into the culture medium and was associated with the extracellular matrix. In addition, increased expressions of beta-catenin and cyclin D1 were observed in cells overexpressing SFRP2. The marked differential expression of SFRP2 reveals that this protein may be a potential candidate marker for CMTs. The CMT cell line established in this study provides a useful tool and experimental model for understanding both the tumorigenesis of CMTs and the role of Wnt signaling in cancers. 相似文献
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Rajkumar L Balasubramanian K Arunakaran J Govindarajulu P Srinivasan N 《Cell biology international》2006,30(2):164-168
Estradiol plays a vital role in the growth and development of mammary glands. It is a potent stimulator of metabolic processes in normal and carcinoma breast. A critical factor in determining mammary glandular morphology is the stroma. Collagen is a predominant component of the extracellular matrix and cell-collagen interactions are essential carcinogenesis. The present investigation explored the influence of estradiol on collagen solubility and metabolism in mammary tumors during tumor progression and regression. A single injection of 20 mg of 9,10-dimethyl-1,2-benzanthracene was given to rats at 7 weeks of age. With the appearance of the first palpable mammary tumor, the rats were treated with 0.5 microg estradiol or 50 microg tamoxifen daily for 30 days. The rats were sacrificed 24 h after 30 days of treatment. Estradiol appears to stimulate the synthesis of new collagens and thus contributes to the enlargement of the mammary tumors. This might have created a potential microenvironment by increasing the synthesis of suitable matrix that sustains the growth of the mammary tumors. In short, the present findings emphasize a definite mediatory role for collagen in estradiol promoted mammary tumor growth. 相似文献
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Five different mouse mammary tumor cell lines were propagated in a serum free medium. Evaluation of growth characteristics, including logarithmic growth, cell population increase, protein production and days to confluency, showed serum-free medium comparable to serum-containing medium. Mouse mammary tumor virus expression and production, in C3H and GR tumor cell lines, as determined by virus particle counting and RNA dependent DNA polymerase assays, subsequent to dexamethasone stimulation revealed equivalent to higher levels of virus in serum-free medium as compared to serum-containing medium. 相似文献
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An established R3 mouse mammary tumor cell line; kinetics of mammary tumor virus (MTV) production 总被引:4,自引:0,他引:4
E Y Lasfargues B Kramarsky N H Sarkar J C Lasfargues D H Moore 《Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.)》1972,139(1):242-247
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Frank Maldarelli Mary Jane Yagi 《In vitro cellular & developmental biology. Plant》1986,22(9):542-548
Summary The MJY-alpha epithelial-like mammary tumor cell line was adapted for cultivation in suspension using a shaker culture technique.
Replication of suspension (MJY-beta) cells was more sensitive than monolayer cells to decreases in the concentration of serum
in the medium. Comparison of amino acid incoerporation and lactate production rates revealed additional differences between
monolayer and suspension cultures. In addition, growth in susfpension resulted in 10- to 400-fold increases in mouse mammary
tumor virus (MMTV) production by the mammary tumor cells. Incrases in MMTV yield were detected within 48 h of culture initiation
and MMTV production remained elevated throughout 20 cell passages in suspension. Exposure of MJY-beta cells to 14 μM hydrocorticone further increased MMTV yield two-to five-fold. The MJY-beta suspension cultures demonstrated that these epithelial-like
cells do not require attachment to a solid substrate for replication or for MMTV production. Loss of structural polarization
associated with growth as a monolayer resulted in stimulation of MMTV production greater than and independent of steroid exposure.
This work was supported by the T. J. Martell Foundation for Cancer and Leukemia Research and by USPHS grant 5P-30CA23102.
F. M. is a trainee on MSTP grant GM07280 from the National Institute of Health. This work was submitted in partial fullfillment
of the requirements for the Ph. D. degree (F. M.). 相似文献