Suppression Role of Androgen-Response Gene Calreticulin in Prostate Cancer

摘要

Androgens are intimately associated with prostate cancer progression. We have previously identified more than 24 androgen-response genes. One of the genes encodes calreticulin, a highly conserved protein with demonstrated functions in intracellular Ca(++) homeostasis, cell adhesion, chaperoning, and gene expression. Our studies have indicated that calreticulin overexpression is suppressive to anchorage-independent growth and metastasis of prostate cancer cells and calreticulin expression is down-regulated in human prostate tumor specimens. Thus, down-regulation of calreticulin in clinical prostate cancer specimens is likely to be an important step in prostate cancer progression. Our observations argue that part of androgen-induced gene expression program, such as calreticulin, is inactivated in the progression of prostate cancer, which represents a new concept in prostate cancer biology. Our results also provided strong basis for further exploring the mechanism by which calreticulin suppresses prostate tumor metastasis. In addition, we have generated several mutants for calreticulin, which will allow us to determine which of the three domains, N, P, or C, is responsible for the suppression of prostate tumor metastasis.