The Function Of Mitochondrial Protein Brp44l In Breast Cancer

Certain proteins are over-expressed and others are downregulated in breast cancer tumorigenesis and metastasis. We can identify specific tumor biomarkers by comparing the difference of expressed proteins between normal and tumor samples, which may result in more effective therapeutics for cancer treatment. The proteins involved in breast cancer initiation and progression are still largely elusive. To gain insights into these processes, we conducted quantitative proteomic analyses with 21T series of beast cell lines, which include a normal, primary tumor and a metastatic tumor that were isolated from a single patient. Stable isotope labeling of amino acid in cell culture followed by LC-MS/MS analysis was performed and deregulated proteins were identified using statistical analysis. Gene ontology analysis revealed that proteins involved in metabolic processes were the most deregulated in both tumorigenesis and metastasis. Interaction network analysis indicated the ERBB2 signaling played a critical role in tumorigenesis. In addition to known markers such as ERBB2 and E-cadherin, novel markers, including BRP44L, MTHFD2 and TIMM17A, were found to be overexpressed in 21T breast cancer cells and verified in additional breast cell lines. More interestingly, shRNA knockdown experiments indicated an oncogenic activity of BRP44L in breast cancer. Our study provides a list of potential novel markers for breast cancer tumorigenesis and metastasis using a unique cell model. Further studies on BRP44L as well as other markers on the list may reveal mechanisms that result in more effective therapeutics for cancer treatment.Breast cancer is the most common type of cancer in women worldwide. In recent years, the incidence of breast cancer has increased dramatically in our country due to a variety of factors, such as environmental changing, population growth and aging. But the studies of tumor biomarkers in breast cancer initiation and progression are still quite primitive. Modern cytogenetics and molecular biology research reveals that the occurrence and development of tumor are complicated multivariate, multigene and multistage processes. These processes and the proteins involved warrant further research.Our study found that the expression of BRP44L (brain protein 44-like) was significantly increased with of the increase of tumor malignancy. To investigate the function of BRP44L in breast carcinoma, we established a shRNA lentivirus expression system, and inhibited expression of BRP44L in three breast cancer cell lines, i.e. MDA-MB-231, MCF-7 and T47D. We found that these cell lines showed a strong inhibition ofgrowth and survival after the knockdown treatments. These findings suggest that BRP44L play an important role in the occurrence and development of breast carcinoma and implies that BRP44L could be a useful molecular target for breast cancer therapy.We approached biomarker discovery for breast cancer progression with quantitative proteomics strategies in a special cell line model, and SILAC strategy was utilized to obtain a comprehensive list of proteins that were deregulated during tumorigenesis and metastasis, some of which are potential novel markers for breast cancer. Our research studies the function of one novel marker protein, mitochondrial protein Brp441 in breast cancer by using the shRNA lentivirus expression system. The results suggest BRP44L may be a potential target for the therapy of breast carcinoma.