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
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.