IMMORTALIZATION OF DISTINCT HUMAN MAMMARY EPITHELIAL-CELL TYPES BY HUMAN PAPILLOMA-VIRUS-16 E6 OR E7

Citation
De. Wazer et al., IMMORTALIZATION OF DISTINCT HUMAN MAMMARY EPITHELIAL-CELL TYPES BY HUMAN PAPILLOMA-VIRUS-16 E6 OR E7, Proceedings of the National Academy of Sciences of the United Statesof America, 92(9), 1995, pp. 3687-3691
Citations number
23
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Multidisciplinary Sciences
ISSN journal
0027-8424
Volume
92
Issue
9
Year of publication
1995
Pages
3687 - 3691
Database
ISI
SICI code
0027-8424(1995)92:9<3687:IODHME>2.0.ZU;2-#
Abstract
Multiple mammary epithelial cell (MEG) types are observed both in mamm ary ducts in vivo and in primary cultures in vitro; however, the oncog enic potential of different cell types remains unknown. Here, we used human papilloma virus 16 E6 and E7 oncogenes, which target p53 and Rb tumor suppressor proteins, respectively, to immortalize MECs present i n early or late passages of human mammary tissue-derived cultures or i n milk. One MEC subtype was exclusively immortalized by E6; such cells predominated in late-passage cultures but were rare at early passages and apparently absent in milk, Surprisingly, a second cell type, pres ent only in early-passage tissue-derived cultures, was fully immortali zed by E7 alone, A third cell type, observed in tissue-derived culture s and in milk, showed a substantial extension of life span with E7 but eventually senesced. Finally, both E6 and E7 were required to fully i mmortalize milk-derived MECs and a large proportion of MECs in early-p assage tissue derived cultures, suggesting the presence of another dis crete subpopulation. Identification of MECs with distinct susceptibili ties to p53- and Rb-targeting human papillomavirus oncogenes raises th e possibility that these cells may serve as precursors for different f orms of breast cancer.