Testin is a tumor suppressor and prognostic marker in breast cancer

Abstract

The testin (TES) gene was previously identified in the fragile chromosomal region FRA7G at 7q31.2. In the present study, we aimed to investigate the candidate tumor suppressor function of TES and explore its correlations to clinicopathologic features and prognosis in breast cancer. In clinical samples, we showed that the expression of TES decreased gradually from normal through ductal hyperplasia without atypia, atypical ductal hyperplasia, and ductal carcinoma in situ, to invasive ductal carcinoma. To explore the possible tumor suppressing function of TES, the expression of TES in breast cancer cells was manipulated by ectopic expression or by RNAi. We revealed that ectopic TES expression significantly inhibited cell proliferation, invasive ability, and angiogenesis, whereas knockdown of TES by RNAi enhanced cell proliferation, invasive ability, and angiogenesis. In an animal model, TES markedly inhibited breast cancer cell xenograft formation in athymic nude mice and reduced breast cancer cell metastasis to lung. Moreover, we revealed that TES inhibited the invasion and angiogenesis of breast cancer partially through miR-29b-mediated MMP-2 inhibition. Using the tissue microarray of breast cancer from Yale University, we found that lower TES expression was an independent prognostic factor for shorter overall survival and disease-free survival with univariate and multivariate analyses. Taken together, these data suggest that TES, as a valuable marker of breast cancer prognosis, plays an important role in the development and progression of breast cancer. TES may be an effective novel target in breast cancer prevention and treatment.