ABSTRACT
Autophagy is a cellular process that plays a major role in the fate of tumor cells. Understanding the role of autophagy in cancer therapy is a major challenge, particularly for breast cancer as the sole top cause of mortality among women. In this study, we evaluated the gene expression of mTOR and Beclin1 and the levels of p62 protein, in breast tumors and compared them to a control condition. To explore the role of autophagy in breast cancer, we acquired tumor biopsies from 41 new cases of breast cancer patients. We extracted total RNA from each biopsy and used real-time PCR to quantify Beclin1 and mTOR-specific RNA expression. In addition, we evaluated the expression of the p62 protein in paraffin-embedded tumor tissue using the immunohistochemistry technique. The data revealed an upregulation of Beclin1 and a downregulation of mTOR in tumor tissues compared to the control condition. The correlation between p62 expression and Beclin1/mTOR showed a negative and positive correlation, respectively, confirming autophagy activation in the tumor tissues. However, there was no correlation between autophagy markers and tumor size, grade and stage. The findings revealed that autophagy activation was found in breast tumor tissues, suggesting that autophagy can be a target for breast cancer therapy.
ABSTRACT
OBJECTIVE: Breast cancer is the leading cause of death among women in many countries. Numerous factors serve as oncogenes or tumor suppressors in breast cancer. The large family of Tripartite-motif (TRIM) proteins with ~ 80 members has drawn attention for their role in cancer. TRIM3 and TRIM16 have shown suppressive activity in different cancers. This study aimed to evaluate the expression of TRIM3 and TRIM16 in cancerous and normal breast samples and to investigate their association with different clinical and pathological parameters. RESULTS: qRT-PCR was utilized to determine the gene expression of TRIM3 and TRIM16. The expression of TRIM3 and TRIM16 genes in tumor samples were significantly reduced to 0.45 and 0.29 fold, respectively. TRIM3 and TRIM16 genes expression were both positively correlated with the invasion of breast cancer. TRIM3 gene expression was associated with tumors' histological grade. However, no significant association was found between the expression of the genes and tumor size, stage and necrosis. The expression of TRIM3 and TRIM16 are significantly reduced in breast cancer tissues. Besides, the expression of both TRIM3 and TRIM16 genes significantly plummet in lymphatic/vascular and perineural invasive samples. Hence, we suggest a potential tumor suppressor role for TRIM3 and TRIM16 in breast cancer.
