Characterization of a Tissue-specific CDP/Cux Isoform, p75, Activated in Breast Tumor Cells

作者: Sarkis Meterissian , Lam Leduy , Madeleine Poirier , Ginette Bérubé , Peter Watson

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摘要: Two isoforms of the CCAAT-displacement protein/cut homeobox (CDP/Cux) transcription factor have been characterized thus far. The full length protein, p200, which contains four DNA binding domains, transiently binds to and carries activity. p110 isoform is generated by proteolytic processing at G1-S transition capable stable interaction with DNA. Here we demonstrate existence a shorter CDP/Cux isoform, p75, only two Cut repeat 3 homeodomain, more stably p75 was able repress reporter carrying promoter for cyclin-dependent kinase inhibitor p21 gene activate polymerase alpha reporter. Expression involved novel mechanism: initiation within intron 20. 20-initiated mRNA (I20-mRNA) expressed higher level in thymus CD4+/CD8+ CD4+ T cells. I20-mRNA weakly or not all normal human mammary epithelial cells breast tissues but detected many tumor lines tumors. In invasive tumors significant association established between expression diffuse infiltrative growth pattern (n = 41, P 0.0137). agreement these findings, T47D cancer expressing could form tubule structures collagen rather developed as solid undifferentiated aggregates Taken together, results suggest that aberrant may be associated process tumorigenesis cancer.

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