Loss of p16INK4 expression by methylation is associated with lifespan extension of human mammary epithelial cells
Language: 
English
Abstract: 

Inactivation of p16INK4 tumor suppressor gene function is frequently observed in breast cancer. We examined p16INK4 expression in human mammary epithelial cell (HMEC) cultures established from four normal donors. Normal HMECs divide a limited number of times before proliferation ceases in a state referred to as selection (or M0). The cell subpopulation that emerges spontaneously from selection undergoes a further limited period of proliferation before senescence. By immunofluorescence and Western blot analysis of four independent cultures, we have shown loss of p16INK4 expression in postselection HMECs. In contrast, p16INK4 was present in both early and late passage fibroblasts from the same individuals. Bisulfite genomic sequencing revealed extensive methylation of the p16INK4 CpG island in post- but not preselection cells. Thus, the extended period of growth observed in postselection HMECs is associated with hypermethylation of the p16INK4 CpG island and loss of p16INK4 expression. Although postselection HMECs are widely considered to be normal, these data indicate that they have sustained an epigenetic alteration.

Author(s): 
Huschtscha, L. I.
Noble, J. R.
Neumann, A. A.
Moy, E. L.
Barry, P.
Melki, J. R.
Clark, S. J.
Reddel, R. R.
Item Type: 
Journal Article
Publication Title: 
Cancer Research
Journal Abbreviation: 
Cancer Res.
Publication Date: 
8/15/1998
Publication Year: 
1998
Pages: 
3508-3512
Volume: 
58
Issue: 
16
ISSN: 
0008-5472
Library Catalog: 
NCBI Published Medical (?)
Extra: 
PMID: 9721850

Turabian/Chicago Citation

L. I. Huschtscha, J. R. Noble, A. A. Neumann, E. L. Moy, P. Barry, J. R. Melki, S. J. Clark and R. R. Reddel. 8/15/1998. "Loss of p16INK4 expression by methylation is associated with lifespan extension of human mammary epithelial cells." Cancer Research 58: 16: 3508-3512.

Wikipedia Citation

<ref> {{Cite journal | doi = | issn = 0008-5472 | volume = 58 | pages = 3508-3512 | last = Huschtscha | first = L. I. | coauthors = Noble, J. R., Neumann, A. A., Moy, E. L., Barry, P., Melki, J. R., Clark, S. J., Reddel, R. R. | title = Loss of p16INK4 expression by methylation is associated with lifespan extension of human mammary epithelial cells | journal = Cancer Research | date = 8/15/1998 | pmid = | pmc = }} </ref>