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Culture Models of Human Mammary Epithelial Cell Transformation (2000)

Stampfer, Martha R. ; Yaswen, Paul

Springer

Journal of mammary gland biology and neoplasia 5 (2000), S. 365-378

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ISSN: 1573-7039

Keywords: Immortality ; senescence ; conversion ; telomerase ; TGFβ

Source: Springer Online Journal Archives 1860-2000

Topics: Medicine

Notes: Abstract Human pre-malignant breast diseases, particularly ductal carcinoma in situ (DCIS)3 already display several of the aberrant phenotypes found in primary breast cancers, including chromosomal abnormalities, telomerase activity, inactivation of the p53 gene, and overexpression of some oncogenes. Efforts to model early breast carcinogenesis in human cell cultures have largely involved studies of in vitro transformation of normal finite lifespan human mammary epithelial cells (HMEC) to immortality and malignancy. We present a model of HMEC immortal transformation consistent with the known in vivo data. This model includes a recently described, presumably epigenetic process, termed conversion, which occurs in cells that have overcome stringent replicative senescence and are thus able to maintain proliferation with critically short telomeres. The conversion process involves reactivation of telomerase activity, and acquisition of good uniform growth in the absence and presence of TGFβ. We propose that overcoming the proliferative constraints set by senescence, and undergoing conversion, represent key rate-limiting steps in human breast carcinogenesis, and occur during early stage breast cancer progression.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1023/A:1009525827514

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Properties of epithelial cells cultured from human carcinomas and nonmalignant tissues (1979)

Smith, Helene S. ; Hackett, Adeline J. ; Riggs, John L. ; [et al.]

New York, N.Y. : Wiley-Blackwell

Journal of Supramolecular Structure 11 (1979), S. 147-166

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ISSN: 0091-7419

Keywords: carcinoma and nonmalignant cells ; fibronectin ; human epithelial cells ; plasminogen activator ; Life Sciences ; Molecular Cell Biology

Source: Wiley InterScience Backfile Collection 1832-2000

Topics: Biology , Chemistry and Pharmacology , Medicine

Notes: Human epithelial cell cultures were examined for expression of plasminogen activator and fibronectin matrix. All of the cells examined showed ultrastructural evidence suggesting their epithelial origin, including microvilli and specialized junctions. The nonmalignant cells were also negative for endothelial cell markers (ie, they lacked factor VIII antigen, a nonthrombogenic surface and Weibel-Palade bodies). The nonmalignant lines all produced large amounts of plasminogen activator, whereas the tumor-derived lines showed a gradation of activities, ranging from lines having as much activity as the nonmalignant lines to lines having little or no activity above background. For both normal and malignant cells, addition of dexamethesone only slightly decreased the levels of plasminogen activator. By immunofluorescence microscopy, normal bladder and fetal intestine epithelial cells showed fibronectin in a globular and fibrillar matrix. In contrast, normal mammary epithelial cells had a much diminished amount of fibronectin with a punctate distribution.

Additional Material: 8 Ill.