Suppressive Role of Androgen-Response Gene Calreticulin in Prostate Cancer

摘要

Androgens are intimately associated with prostate cancer progression. One of the androgen-response genes encodes calreticulin, a highly conserved protein with demonstrated functions in intracellular Ca++ homeostasis, cell adhesion, chaperoning, and gene expression. Our studies showed that calreticulin overexpression is suppressive to tumor growth and metastasis of prostate cancer cells in orthotopic and subcutaneous xenograft tumor models and calreticulin expression is down-regulated in human prostate tumor specimens. Thus, down-regulation of calreticulin in clinical prostate cancer specimens is 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. In the present study, we have shown that the proline-rich P-domain, which is thought to have lectin-like chaperoning activity, is responsible for the suppression of prostate tumor growth. Our results provide strong basis for further exploring the mechanism by which calreticulin suppresses prostate tumor progression.