The Overexpression of Myelin and Lymphocyte Protein (MAL) Downregulates MUC1 and Enhances Cisplatin Sensitivity in...

The epigenetic repression of myelin and lymphocyte protein gene (MAL) and over-expression of MUC1 protein are two well-documented hallmarks of various carcinomas including lung cancer. The purpose of this work was to investigate whether ectopic expression of MAL could modify the proliferative activity of MUC1 in human lung adenocarcinoma HCC827 cells. We generated stable HCC827 cell lines, expressing GFP- or myc-MAL constructs, then, followed the expression of MUC1 by RT-qPCR and Western blot, and tested proliferation and sensitivity of those cells to cisplatin. Our results showed that ectopic expression of MAL nearly eliminated cellular levels of MUC1-C. This effect is primarily due to down-regulation of MUC1 expression, as confirmed by RT-qPCR. Additionally, lysosomal-associated degradation of MUC1 may also contribute, as observed when the cells were treated with ammonium chloride and chloroquine. The reduced quantity of MUC1-C negatively affected both cyclin D1 and c-Myc, protein levels, which are linked to cell-proliferative signals involving MUC1-C. Furthermore, expression of MAL decreased the viability of HCC827 cells, and increased their sensitivity to cisplatin. MAL and MUC1 showed an antagonistic relationship in cancer cells, and these findings provide new insights with respect to the regulation of MUC1 and a better understanding of MAL as a potential tumor suppressor.