A novel hormonally-regulated protein with a tetratricopeptide repeat that is over-expressed in breast tumor Free

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Estrogen and progesterone play critical roles in breast cancer biology. Their functions are modulated by their specific receptor estrogen receptor (ER) and progesterone receptor (PR), respectively. Recent studies suggest that heat shock proteins and other cellular chaperones such as FKBP51 and FKBP52 may function to modulate the receptor conformation so as to facilitate or suppress high affinity binding with their ligand. We describe here a new hormonally-regulated protein that exhibits high homology to FKBP-type family protein at the tetratricopeptide repeat domains. KIAA0227 was a hypothetical protein. Polyclonal antibody against the purified protein identified a 24 kD protein that is in line with its prediction. This hypothetical protein is therefore named as TPRp24. Northern blot analysis revealed a ∼2.6 kb transcript that is abundant in ER and PR-positive breast cancer cell lines but undetectable in ER and PR-negative cells. The mRNA and protein levels of the TPRp24 are dramatically up-regulated by progesterone in PR-transfected breast cancer cells MDA-MB-231cells. In MCF-7 cells, the TPR p24 protein is down-regulated by treatment with estrogen, or estrogen plus progesterone. More notably, its mRNA is significantly over-expressed in breast cancer tissues compared with the adjacent normal breast tissue (p = 0.000). Although the exact functions of KIAA0227 in breast cancer remain to be determined, these findings suggest that the TPRp24 is an important gene involved in hormonal signaling and breast cancer development.