Suppressive Roles of Calreticulin in Prostate Cancer Growth and Metastasis
AUTOR(ES)
Alur, Mahesh
FONTE
American Society for Investigative Pathology
RESUMO
Calreticulin is an essential, multifunctional Ca2+-binding protein that participates in the regulation of intracellular Ca2+ homeostasis, cell adhesion, and chaperoning. Calreticulin is abundantly expressed and regulated by androgens in prostate epithelial cells. Given the importance of both calreticulin in multiple essential cellular activities and androgens in prostate cancer, we investigated the possibility of a role for calreticulin in prostate cancer progression. Immunohistochemistry revealed the down-regulation of calreticulin in a subset of human prostate cancer specimens. Prostate cancer cells overexpressing exogenous calreticulin produced fewer colonies in both monolayer culture and soft agar. Furthermore, calreticulin overexpression also inhibited tumor growth in the orthotopic PC3 xenograft tumor model and macroscopic lung metastasis in the rat Dunning AT3.1 prostate tumor model. To address the potential mechanism of calreticulin suppression of prostate cancer, we generated calreticulin mutants with different functional domains deleted. The calreticulin mutants containing the P-domain, which binds to other endoplasmic reticulum chaperone proteins, were sufficient for the suppression of PC3 growth in colony formation assays. Overall, our data support the hypothesis that calreticulin inhibits growth and/or metastasis of prostate cancer cells and that this suppression requires the P-domain.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2716982Documentos Relacionados
- Maspin expression inhibits osteolysis, tumor growth, and angiogenesis in a model of prostate cancer bone metastasis
- Cancer-related changes in prostate DNA as men age and early identification of metastasis in primary prostate tumors
- Prostate-specific membrane antigen can promote in vivo osseous metastasis of prostate cancer cells in mice
- Biological roles of filamin a in prostate cancer cells
- Roles for Nkx3.1 in prostate development and cancer