RESUMO
Recent evidence has demonstrated that A kinase interacting protein 1 (AKIP1), a molecular regulator of protein kinase A, was overexpressed in breast cancer. However, the prognostic and biological role of AKIP1 in breast cancer is still elusive. The purpose of our study was to elucidate the role and molecular mechanism of AKIP1 in breast cancer development. The mRNA levels of AKIP1 in breast cancer and paired normal breast tissues were examined by quantitative real-time PCR. The relationship of AKIP1 expression with clinicopathological characteristics and clinical prognosis of breast cancer patients was investigated. In vitro migration and invasion assays were performed in MCF-7 and SK-BR-3 cells to determine its role in metastasis and the possible mechanism. The result showed that AKIP1 expression was up-regulated in breast cancer tissues compared with that in normal breast tissues. High expression of AKIP1 was associated significantly with advanced tumor stage (P<0.001), tumor size (P=0.029), and lymph node metastasis (P=0.004). Moreover, overexpression of AKIP1 was significantly correlated with poor overall survival and recurrence-free survival (P=0.038 and P=0.005, respectively). Furthermore, down-regulation of AKIP1 remarkably inhibited breast cancer cell motility and invasion through inhibiting the Akt/GSK-3ß/Snail pathway. Therefore, AKIP1 may represent a prospective prognostic indicator and a potential therapeutic target of breast cancer.
RESUMO
BACKGROUND: To investigate the expression and role of PBRM1 in breast cancer, and to evaluate the clinical and prognostic significance of PBRM1 protein in patients with breast cancer. METHODS: The expression of PBRM1 was examined in breast cancer tissue and paired non-cancerous tissues by real-time PCR. Moreover, PBRM1 protein expression was evaluated by immunohistochemistry in 150 paraffin-embedded breast cancer specimens. The correlation between PBRM1 expression and clinicopathological features were statistically analyzed. RESULTS: The status of PBRM1 protein in breast cancer tissues is much lower than that in paracarcinoma tissues. Low PBRM1 expression was positively correlated with tumor stage (P =0.003) and lymph node metastasis (P =0.013). The overall (P =0.003) and recurrent-free survival (P =0.001) of the patients with high PBRM1 expression was significantly lower than the low PBRM1 expression group. Multivariate analysis showed that the expression of PBRM1 was an independent factor of overall survival for the patients with breast cancer (P =0.030). CONCLUSIONS: PBRM1 might involve in the development and progression of breast cancer as a tumor suppressor, and thereby may be a valuable prognostic marker for breast cancer patients.