Abstract：
:Cultures of human mammary epithelial cells (HMECs) contain a subpopulation of variant cells with the capacity to propagate beyond an in vitro proliferation barrier. These variant HMECs, which contain hypermethylated and silenced p16(INK4a) (p16) promoters, eventually accumulate multiple chromosomal changes, many of which are similar to those detected in premalignant and malignant lesions of breast cancer. To determine the origin of these variant HMECs in culture, we used Luria-Delbrück fluctuation analysis and found that variant HMECs exist within the population before the proliferation barrier, thereby raising the possibility that variant HMECs exist in vivo before cultivation. To test this hypothesis, we examined mammary tissue from normal women for evidence of p16 promoter hypermethylation. Here we show that epithelial cells with methylation of p16 promoter sequences occur in focal patches of histologically normal mammary tissue of a substantial fraction of healthy, cancer-free women.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Holst CR,Nuovo GJ,Esteller M,Chew K,Baylin SB,Herman JG,Tlsty TDsubject
Has Abstractpub_date
2003-04-01 00:00:00pages
1596-601issue
7eissn
0008-5472issn
1538-7445journal_volume
63pub_type
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