title: Suppressive roles of calreticulin in prostate cancer growth and metastasis.
abstract: Calreticulin is an essential, multifunctional Ca(2+)-binding protein that participates in the regulation of intracellular Ca(2+) 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.
authors.affiliation: Department of Urology, University of Pittsburgh, 5200 Centre Ave., Shadyside Medical Center, Suite G40, Pittsburgh, PA 15232, USA.
authors.forename: Mahesh
authors.initials: M
authors.lastname: Alur
authors.forename: Minh M
authors.initials: MM
authors.lastname: Nguyen
authors.forename: Scott E
authors.initials: SE
authors.lastname: Eggener
authors.forename: Feng
authors.initials: F
authors.lastname: Jiang
authors.forename: Soheil S
authors.initials: SS
authors.lastname: Dadras
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Stern
authors.forename: Simon
authors.initials: S
authors.lastname: Kimm
authors.forename: Kim
authors.initials: K
authors.lastname: Roehl
authors.forename: James
authors.initials: J
authors.lastname: Kozlowski
authors.forename: Michael
authors.initials: M
authors.lastname: Pins
authors.forename: Marek
authors.initials: M
authors.lastname: Michalak
authors.forename: Rajiv
authors.initials: R
authors.lastname: Dhir
authors.forename: Zhou
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000818:Animals; D037282:Calreticulin / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D006801:Humans; D008171:Lung Diseases / Q000473:pathology; D008297:Male; D051379:Mice; D009154:Mutation; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000473:pathology*; D017434:Protein Structure, Tertiary; D051381:Rats; D023041:Xenograft Model Antitumor Assays
chemical_list: D037282:Calreticulin