An investigation of HtrA gen family gene expression levels in breast cancer and immunohistochemically determination of HtrA proteins in archive materials

Breast cancer affects mainly women and the leading cause of women mortality in many countries. The breast cancer is many ways sporadic and the hereditary type breast cancer constitutes about 20% in many populations. High temperature requirement factor A (HtrA) family proteins are serin protease family proteins. The HtrA family proteins include HtrA1, HtrA2, HtrA3 and HtrA4. HtrA gene family and are associated with developmental stage of the organisms, they play important roles for maintaining their viability and development. Some members of mamalian HtrA proteins are described as potantial modulators of apoptosis and chemotherapy-induced cytotoxicity. With this project it is aimed to determine HtrA gene family mRNA expression levels and proteins in cancereus tissues of patients removed surgically. The gene family mRNA expression levels were determined using RT-PCR in addition to their associated protein levels that were determined by immunohistochemical procedures using corresponding antibodies. The study was designed to analyze 53 patients fresh tissues that are removed surgically and stored -80 0C until their use. The cancerous regions were seperated from the healthy regions by pathological examinations of slices followed by molecular and immunohistochemical analysis. The obtained results were evaluated statistically in order to find out relationship with the HtrA gene family expression and protein levels in tissues with regard to their cancer stages. HtrA2va.1 and HtrA2 mRNA levels were decreased significantly from G1 to G3 stage and from premenaposal to postmenaposal respectively. However these findings by itself is not sufficient to conclude on the impairment of apoptotic pathway by the reduction of HtrA family protein levels. Therefore, inhibitors of IAP family as well as other metabolites needed to be determined about the functional capability of apoptotic pathway in breast cancer. In conclusion, the question remains to be delienated for uncontrolable proliferation aspect of cancer cells that leads to deliterious cancerous tissues.