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首页> 美国政府科技报告 >Telomerase Induction of TGFbeta Resistant Growth in Cultured Human Mammary Epithelial Cells
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Telomerase Induction of TGFbeta Resistant Growth in Cultured Human Mammary Epithelial Cells

机译：端粒酶诱导培养的人乳腺上皮细胞TGFbeta抗性生长

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The failures to growth arrest in response to critically short telomeres or to TGF beta are key derangements thought to contribute to the inappropriate cell growth that characterizes breast cancer progression. Our recent observations indicate that activation of telomerase activity may be directly involved in overcoming both inhibitory pathways in human mammary epithelial cells (HMEC). By exploring the common thread connecting telomerase expression and resistance to TGF beta growth inhibition, it may be possible to unify two divergent areas of significance for breast cancer development and treatment. We have begun to dissect the complex mechanisms responsible for these changes in expectation that such knowledge may enable us to prevent or reverse them. Our work thus far indicates that altered regulation of a well-known oncogene, c-myc, may link these processes by lowering the external signaling requirements for cell proliferation. It is not yet clear, however, how hTERT expression leads to altered c-myc regulation. The ability of the hTERT protein to cause TOF % resistance does not appear to be separable from its ability to bind and lengthen telomeres in vivo. The ability of hTERT to cause TGF beta resistance depends on cell context; only HMEC lacking pl6 expression were susceptible to hTERT immortalization and TGF beta resistance. This suggests that particular cell types may be targeted in vivo.

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