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Title: Culture models of human mammary epithelial cell transformation

Abstract

Human pre-malignant breast diseases, particularly ductal carcinoma in situ (DCIS)3 already display several of the aberrant phenotypes found in primary breast cancers, including chromosomal abnormalities, telomerase activity, inactivation of the p53 gene and overexpression of some oncogenes. Efforts to model early breast carcinogenesis in human cell cultures have largely involved studies in vitro transformation of normal finite lifespan human mammary epithelial cells (HMEC) to immortality and malignancy. We present a model of HMEC immortal transformation consistent with the know in vivo data. This model includes a recently described, presumably epigenetic process, termed conversion, which occurs in cells that have overcome stringent replicative senescence and are thus able to maintain proliferation with critically short telomeres. The conversion process involves reactivation of telomerase activity, and acquisition of good uniform growth in the absence and presence of TFGB. We propose th at overcoming the proliferative constraints set by senescence, and undergoing conversion, represent key rate-limiting steps in human breast carcinogenesis, and occur during early stage breast cancer progression.

Authors:
;
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Director, Office of Science. Office of Biological and Environmental Research. Life Sciences Division; National Institutes of Health (US)
OSTI Identifier:
834483
Report Number(s):
LBNL-47123
R&D Project: 863612; TRN: US200432%%355
DOE Contract Number:  
AC03-76SF00098
Resource Type:
Journal Article
Resource Relation:
Journal Name: Journal of Mammary Gland Biology and Neoplasia; Journal Volume: 5; Journal Issue: 4; Other Information: Journal Publication Date: 10/2000; PBD: 10 Nov 2000
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 98 NUCLEAR DISARMAMENT, SAFEGUARDS, AND PHYSICAL PROTECTION; ANIMAL CELLS; CARCINOGENESIS; CARCINOMAS; CELL TRANSFORMATIONS; DISEASES; GENES; IN VITRO; IN VIVO; INACTIVATION; MAMMARY GLANDS; NEOPLASMS; ONCOGENES; PROLIFERATION; TELOMERES; TRANSFORMATIONS; IMMORTALITY SENESCENCE CONVERSION TELOMERASE TGFB

Citation Formats

Stampfer, Martha R., and Yaswen, Paul. Culture models of human mammary epithelial cell transformation. United States: N. p., 2000. Web. doi:10.1023/A:1009525827514.
Stampfer, Martha R., & Yaswen, Paul. Culture models of human mammary epithelial cell transformation. United States. doi:10.1023/A:1009525827514.
Stampfer, Martha R., and Yaswen, Paul. Fri . "Culture models of human mammary epithelial cell transformation". United States. doi:10.1023/A:1009525827514.
@article{osti_834483,
title = {Culture models of human mammary epithelial cell transformation},
author = {Stampfer, Martha R. and Yaswen, Paul},
abstractNote = {Human pre-malignant breast diseases, particularly ductal carcinoma in situ (DCIS)3 already display several of the aberrant phenotypes found in primary breast cancers, including chromosomal abnormalities, telomerase activity, inactivation of the p53 gene and overexpression of some oncogenes. Efforts to model early breast carcinogenesis in human cell cultures have largely involved studies in vitro transformation of normal finite lifespan human mammary epithelial cells (HMEC) to immortality and malignancy. We present a model of HMEC immortal transformation consistent with the know in vivo data. This model includes a recently described, presumably epigenetic process, termed conversion, which occurs in cells that have overcome stringent replicative senescence and are thus able to maintain proliferation with critically short telomeres. The conversion process involves reactivation of telomerase activity, and acquisition of good uniform growth in the absence and presence of TFGB. We propose th at overcoming the proliferative constraints set by senescence, and undergoing conversion, represent key rate-limiting steps in human breast carcinogenesis, and occur during early stage breast cancer progression.},
doi = {10.1023/A:1009525827514},
journal = {Journal of Mammary Gland Biology and Neoplasia},
number = 4,
volume = 5,
place = {United States},
year = {Fri Nov 10 00:00:00 EST 2000},
month = {Fri Nov 10 00:00:00 EST 2000}
}