Expression of CHAC1 in Breast Cancer Cell Lines

Abstract

Breast cancer is the commonly diagnosed type of cancer in women and is a major cause of deaths in women. Unfolded Protein Response Pathway is a signaling pathway induced in endoplasmic reticulum as a stress response. This type of stress signaling has been seen to be activated in many tumors including breast cancer. CHAC1 (Glutathione specific gamma- glutamylcyclotransferas-1) is a member of UPR Pathway. It was first discovered as a component of the ATF4 arm of the UPR pathway in a co-regulated group of genes. CHAC1 expression is necessary and sufficient to induce well-characterized markers of apoptosis. CHAC1 is involved in the inhibition of TNFRS6B via ATF4-ATF3-CHOP signaling. This sensitizes cells to commit to apoptosis following induction of UPR pathway. Although CHAC1 is a pro-apoptotic component of the UPR pathway, its expression in breast cancers have been noted to be remarkably high. To study the role of CHAC1 in breast cancer, we analyzed the expression of CHAC1 at mRNA level by using Real-Time PCR and further checked its' protein expression by Western-blotting. Its expression was found to be higher in ER positive cells as compared to the ER negative cells. Further investigations were performed by transfecting MDA-MB-231 cells by ER-alpha, which confirmed that presence of ER-alpha leads to the higher expression cHAC1 in breast cancer cells.