The protein expression of Tetratricopeptide Repeat Domain 9 at different stages of mammary development

B49

We have previously reported that tetratricopeptide repeat protein 9 (TTC9) was a progesterone-regulated gene in progesterone receptor (PR)-transfected breast cancer cells MDA-MB-231 and it is also a growth factor-inducible protein. Our results also suggested that TTC9 was a direct PR target gene and was seen to be significantly over expressed in breast cancer tissue compared to normal adjacent tissue. In this study we elucidated the expression profile of TTC9 at various stages of mammary development in female mice. Mammary tissues at pregnant day 10 expressed higher levels of TTC9 in comparison to virgin mice and mice at pregnant day 18 when the mammary gland had already started secretory differentiation. Early lactating mammary gland (day 2 post partum) expressed similar levels of TTC9 protein to that at pregnant day 18. There is a gradual increase in TTC9 level as lactation proceeds through and very high level is attained by lactating day 18. Mammary gland undergoing involution also expressed high level of TTC9 protein comparable to that at lactating 18. Interestingly, forced weaning after day 12 lactation caused a sharp rise of TTC9 protein level. Restoration of lactation by replacing the pups again caused a reduction of TTC9 level in the mammary gland. We hypothesized that TTC9 may be involved in mammary tissue remodeling. This is supported by the studies using teat sealing model in which normal lactating gland express considerably lower levels of TTC9 then the teat-sealed glands in the same mice. In conclusion, the protein level of TTC9 is regulated as a function of mammary development. TTC9 expression is negatively associated with secretory state but positively related to mammary involution when the cells undergo apoptosis. The findings provide clues to further elucidate the role of TTC9 in mammary development and its possible involvement in breast cancer.