51435

SCARA3

scavenger receptor class A, member 3;SCARA3;scavenger receptor class A, member 3

cellular stress response gene protein|cellular stress response protein|macrophage scavenger receptor-like 1|scavenger receptor class A member 3

8p21

protein-coding

Scavenger receptor class A, member 3 (SCARA3) was previously found to be overexpressed in ovarian/primary peritoneal carcinoma (OC/PPC) compared with breast carcinoma effusions by global gene expression analysis. The present study aimed to validate this finding applying quantitative PCR and analyzing the association between SCARA3 expression and clinicopathologic parameters in a large OC cohort. SCARA3 messenger RNA (mRNA) expression was analyzed in 127 effusions (103 ovarian/peritoneal/fallopian tube carcinomas, 9 breast carcinomas, 15 malignant mesotheliomas [MM]), and 30 solid primary OCs. The association between OC SCARA3 levels and clinicopathologic parameters was investigated. SCARA3 mRNA was expressed in all effusions, irrespective of tumor type. However, transcript levels were significantly higher in OC compared with breast carcinoma (P < .001) and MM (P = .011) effusions. Primary OCs and effusions had comparable expression levels. Higher SCARA3 expression was found in disease recurrence postchemotherapy compared with primary diagnosis prechemotherapy OC effusions (P = .001), and this difference was significant for treatment with both platinum agents (P = .006) and paclitaxel (P = .002). SCARA3 levels in effusions and primary carcinomas were unrelated to patient age, tumor grade, FIGO stage, residual tumor volume after surgery, response to chemotherapy, or survival (P > .05 for all). In conclusion, SCARA3 mRNA by quantitative PCR is highly expressed in OC and may aid in differentiating this tumor from other cancers, particularly breast carcinoma, in effusions. The consistently high SCARA3 levels in both primary carcinomas and metastatic cells in effusions, and its up-regulation along disease progression from diagnosis to recurrence, suggest a role in ovarian cancer biology.

Prostate cancer is frequent among men over 45 years of age, but it generally only becomes lethal with metastasis. In this study, we identified a gene called cellular stress response 1 (CSR1) that was frequently down-regulated and methylated in prostate cancer samples. Survival analysis indicated that methylation of the CSR1 promoter, and to a lesser extent down-regulation of CSR1 protein expression, was associated with a high rate of prostate cancer metastasis. Forced expression of CSR1 in prostate cancer cell lines DU145 and PC3 resulted in a two- to threefold decrease in colony formation and a 10-fold reduction in anchorage-independent growth. PC3 cells stably expressing CSR1 had an average threefold decrease in their ability to invade in vitro. expression of CSR1 in PC3 cell xenografts produced a dramatic reduction (>8-fold) in tumor size, rate of invasion (0 versus 31%), and mortality (13 versus 100%). The present findings suggest that CSR1 is a potent tumor sup-pressor gene.