Culture models of human mammary epithelial cell transformation
- LBNL Library
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.
- Research Organization:
- Ernest Orlando Lawrence Berkeley National Laboratory, Berkeley, CA (US)
- Sponsoring Organization:
- USDOE Director, Office of Science. Office of Biological and Environmental Research. Life Sciences Division; National Institutes of Health (US)
- DOE Contract Number:
- AC03-76SF00098
- OSTI ID:
- 834483
- Report Number(s):
- LBNL--47123
- Journal Information:
- Journal of Mammary Gland Biology and Neoplasia, Journal Name: Journal of Mammary Gland Biology and Neoplasia Journal Issue: 4 Vol. 5
- Country of Publication:
- United States
- Language:
- English
Similar Records
Investigating YAP’s role in Human Mammary Epithelial Cell (HMEC) Immortalization and Cancer Stem Cell (CSC) Phenotype Acquisition during Early Breast Cancer Progression
Genes involved in immortalization of human mammary cells
Related Subjects
98 NUCLEAR DISARMAMENT, SAFEGUARDS, AND PHYSICAL PROTECTION
ANIMAL CELLS
CARCINOGENESIS
CARCINOMAS
CELL TRANSFORMATIONS
DISEASES
GENES
IMMORTALITY SENESCENCE CONVERSION TELOMERASE TGFB
IN VITRO
IN VIVO
INACTIVATION
MAMMARY GLANDS
NEOPLASMS
ONCOGENES
PROLIFERATION
TELOMERES
TRANSFORMATIONS