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Publication : TSC-22D1 isoforms have opposing roles in mammary epithelial cell survival.

First Author  Huser CA Year  2010
Journal  Cell Death Differ Volume  17
Issue  2 Pages  304-15
PubMed ID  19745830 Mgi Jnum  J:169435
Mgi Id  MGI:4940967 Doi  10.1038/cdd.2009.126
Citation  Huser CA, et al. (2010) TSC-22D1 isoforms have opposing roles in mammary epithelial cell survival. Cell Death Differ 17(2):304-15
abstractText  Transforming growth factor beta (TGFbeta)-stimulated clone-22 domain family member 1 (TSC-22D1) has previously been associated with enhanced apoptosis in several cell systems. In an attempt to identify novel factors that are involved in the control of cell death during mammary gland involution, we found that the mRNA for isoform 2 of TSC-22D1 was highly upregulated 24 h after forced weaning, when a dramatic increase in cell death occurred, closely following the expression of the known inducer of cell death during involution, TGFbeta3. This was paralleled by strongly increased TSC-22D1 isoform 2 protein levels in the luminal epithelium. In contrast, RNA and protein expression levels of the isoform 1 of TSC-22D1 did not change during development. Whereas isoform 2 induced cell death, isoform 1 suppressed TGFbeta-induced cell death and enhanced proliferation in mammary epithelial cell lines. Furthermore, four distinct forms of isoform 2 protein were detected in the mammary gland, of which only a 15-kDa form was associated with early involution. Our data describe novel opposing functions of the two mammalian TSC-22D1 isoforms in cell survival and proliferation, and establish the TSC-22D1 isoform 2 as a potential regulator of cell death during mammary gland involution.
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