Mucin (MUC1) Expression and Function in Prostate Cancer Cells

摘要

Mucin glycoproteins are highly expressed by many tumors, reduce normal cell-cell and cell-extracellular matrix adhesion and protect cancer cells from attack by the immune system. Mucin expression not only increases, but also changes from a restricted pattern of apical expression to a general distribution over the entire cell surface. In this regard, conversion of prostate epithelium from a highly-organized, growth-controlled phenotype to a highly proliferative, metastatic phenotype is associated with loss of cell polarity. Very few studies been performed on mucin expression by prostate cancer cells. MUC1 is a large molecular weight, type I transmembrane mucin glycoprotein expressed by normal and malignant prostate epithelium. High level cell surface expression, reported immunosupressive activities of its released ectodomain, and antiadhesive properties all contribute to this mucin's ability to protect and promote tumor cell growth and survival. Recent observations using human breast cancer cell lines indicate that MUC1 can associate with the intracellular signal transducing molecules, beta-catenin and GRB-2. Recent studies from the PI's lab demonstrate that cytokines, including interferon- gamma, markedly stimulate MUC1 gene expression. Primary prostate tumors are often found in the vicinity of cytokine producing cells, and commonly metastasize to bone marrow, a rich source of these same cytokines.