Abstract:
:A novel human mammary epithelial cell line, HME348, was established from benign breast tissue from a 44-year-old germ-line BRCA2 mutation carrier with a history of stage 1 breast cancer. Mutation analysis showed that the patient had a known 6872del4 BRCA2 heterozygous mutation. The human mammary epithelial cells passaged in culture exhibited cellular replicative aging as evidenced by telomere shortening, lack of telomerase activity, and senescence. Ectopic expression of telomerase (hTERT) reconstituted telomerase activity in these cells and led to the immortalization of the cells. When grown on glass, the majority of immortalized HME348 cells expressed ESA and p63 with a small population also expressing EMA. In three-dimensional Matrigel culture, HME348 cells formed complex branching acini structures that expressed luminal (EMA, CK18) and myoepithelial (p63, CALLA, CK14) markers. Three clones derived from this culture were also p63(+)/ESA(+)/EMA(+/-) on glass but formed similar acinar structures with both luminal and myoepithelial cell differentiation in Matrigel confirming the mammary progenitor nature of these cells. Additionally, the experimentally immortalized HME348 cells formed acini in cleared mammary fat pads in vivo. As this is the first report establishing and characterizing a benign human mammary epithelial cell line derived from a BRCA2 patient without the use of viral oncogenes, these cells may be useful for the study of BRCA2 function in breast morphogenesis and carcinogenesis.
journal_name
Breast Cancer Res Treatjournal_title
Breast cancer research and treatmentauthors
Lewis CM,Herbert BS,Bu D,Halloway S,Beck A,Shadeo A,Zhang C,Ashfaq R,Shay JW,Euhus DMdoi
10.1007/s10549-006-9189-9subject
Has Abstractpub_date
2006-09-01 00:00:00pages
103-15issue
1eissn
0167-6806issn
1573-7217journal_volume
99pub_type
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journal_title:Breast cancer research and treatment
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
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