Normal human mammary epithelial cells spontaneously escape senescence and acquire genomic changes
Romanov, S.R., Kozakiewicz, B.K., Holst, C.R., Stampfer, M.R., Haupt, L.M., & Tlsty, T.D. (2001) Normal human mammary epithelial cells spontaneously escape senescence and acquire genomic changes. Nature, 409(6820), pp. 633-7.
Senescence and genomic integrity are thought to be important barriers in the development of malignant lesions. Human fibroblasts undergo a limited number of cell divisions before entering an irreversible arrest, called senescence. Here we show that human mammary epithelial cells (HMECs) do not conform to this paradigm of senescence. In contrast to fibroblasts, HMECs exhibit an initial growth phase that is followed by a transient growth plateau (termed selection or M0; refs 3-5), from which proliferative cells emerge to undergo further population doublings (approximately 20-70), before entering a second growth plateau (previously termed senescence or M1; refs 4-6). We find that the first growth plateau exhibits characteristics of senescence but is not an insurmountable barrier to further growth. HMECs emerge from senescence, exhibit eroding telomeric sequences and ultimately enter telomere-based crisis to generate the types of chromosomal abnormalities seen in the earliest lesions of breast cancer. Growth past senescent barriers may be a pivotal event in the earliest steps of carcinogenesis, providing many genetic changes that predicate oncogenic evolution. The differences between epithelial cells and fibroblasts provide new insights into the mechanistic basis of neoplastic transformation.
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|Item Type:||Journal Article|
|Additional Information:||Romanov, S R
Kozakiewicz, B K
Holst, C R
Stampfer, M R
Haupt, L M
Tlsty, T D
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.
Nature. 2001 Feb 1;409(6820):633-7.
|Keywords:||Adolescent, Adult, Breast/*cytology/metabolism/ultrastructure, *Cell Aging, Cell Division, Cell Transformation, Neoplastic, Cells, Cultured, Chromosome Aberrations, Epithelial Cells/cytology/ultrastructure, Female, Fibroblasts/cytology, Humans, Karyotyping, Telomere, Tumor Suppressor Protein p53/metabolism|
|ISSN:||1476-4687 (online) 0028-0836 (Print)|
|Subjects:||Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > BIOCHEMISTRY AND CELL BIOLOGY (060100) > Cell Development Proliferation and Death (060103)|
|Divisions:||Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
|Copyright Owner:||Copyright 2001 Macmillan Magazines Ltd.|
|Copyright Statement:||Author's Pre-print: author can archive pre-print (ie pre-refereeing)
Author's Post-print: subject to Restrictions below, author can archive post-print (ie final draft post-refereeing)
Restrictions: •6 months embargo
Publisher's Version/PDF: author cannot archive publisher's version/PDF
|Deposited On:||02 Apr 2014 02:11|
|Last Modified:||07 Apr 2014 02:04|
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