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Old 11-10-2009, 03:55 PM   #53
Rich66
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Re: Cancer stem cells: The root of all evil?

Biol Cell. 2009 Nov 9. [Epub ahead of print]
Modulation of tumorigenesis and estrogen receptor-alpha expression by cell culture condition in a stem cell-derived breast epithelial cell line.

Wang KH, Kao AP, Chang CC, Lee JN, Chai CY, Hou MF, Liu CM, Tsai EM.
Background information. The common phenotypes of cancer and stem cells suggest that cancers arise from stem cells. Estrogen is one of few most important determinants in breast cancer as shown by several convincing evidence. We have previously reported a human breast epithelial cell type (Type 1 HBEC) with stem cell characteristics and estrogen receptor alpha (ERalpha) expression. A tumorigenic cell line, M13SV1R2, was developed from this cell type following SV40 large T-antigen transfection and X-ray irradiation. The cell line, however, was not responsive to estrogen for cell growth or tumor development. In this study, we tested the hypothesis that deprivation of growth factors and hormones may change tumorigenicity and estrogen response of this cell line. Results. The M13SV1R2 cells lost its tumorigenicity after culturing in a growth factor/hormone-deprived medium for <10 passages (referred to as R2d cells) concomitant with the expression of two tumor suppressor genes, maspin and alpha-6 integrin. However, these cells acquired estrogen responsiveness in cell growth and tumor development. By immunocytochemistry, western blotting and flow cytometry analysis, , i.estrogen treatment of R2d cells was found to induce many important effects related to breast carcinogenesise. 1) the emergence of a subpopulation of cells expressing CD44+/high/CD24-/low breast tumor stem cell markers; 2) the induction of EMT; 3) the acquisition of metastatic ability; and 4) the expression of COX-2 through CD44-mediated mechanism. Conclusion. Estrogen responsive cell line with ERalpha and CD44+/CD24-/low expression can be derived from breast epithelial stem cells. The tumorigenicity and estrogen response of these cells could depend on cell culture condition. The findings of this study have implications in regard to the origins of 1) ERalpha-positive breast cancers, 2) CD44+/CD24-/low breast tumor stem cells and 3) metastatic ability of breast cancer.

PMID: 19895368 [PubMed - as supplied by publisher]
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