Tetratricopeptide repeat domain 9 (TTC9) mRNA was drastically up-regulated by progesterone in progesterone receptor-transfected breast cancer cells MDA-MB-231. This up-regulation is coupled with progesterone-mediated growth inhibition and induction of focal adhesion. We have generated mouse polyclonal antibody against a predicted 222 aa TTC9 protein and identified a 25 kDa TTC9 protein that is widely expressed in human tissues, with the highest expression in the brain. Immunostaining and cell fractionation studies revealed that TTC9 is predominantly localized to the endoplasmic reticulum. The level of TTC9 protein in MCF-7 cells is regulated by various factors and chemical reagents including estrogen, progesterone, growth factors, ICI182,780, and p38 kinase inhibitor SB203580. Growth factor-induced TTC9 protein expression was inhibited by estrogen and abolished by ERK inhibitor PD98059. Though the function of TTC9 is not yet clear, the susceptibility of its protein level to biological and chemical agents suggests that TTC9 is a biologically significant protein. (c) 2006 Elsevier Inc. All rights reserved.