Selenium binding protein 1 in ovarian cancer.
Selenium binding protein 1 (SELENBP1) was identified to be the most significantly down-regulated protein in ovarian cancer cells by a membrane proteome profiling analysis. SELENBP1 expression levels in 4 normal ovaries, 8 benign ovarian tumors, 12 borderline ovarian tumors and 141 invasive ovarian cancers were analyzed with immunohistochemical assay. SELENBP1 expression was reduced in 87% cases of invasive ovarian cancer (122/141) and was significantly reduced in borderline tumors and invasive cancers (p<0.001). Cox multivariate analysis within the 141 invasive cancer tissues showed that SELENBP1 expression score was a potential prognostic indicator for unfavorable prognosis of ovarian cancer (hazard ratio [HR], 2.18; 95% CI=1.22-3.90; p=0.009). Selenium can disrupt the androgen pathway, which has been implicated in modulating SELENBP1 expression. We investigated the effects of selenium and androgen on normal human ovarian surface epithelial (HOSE) cells and cancer cells. Interestingly, SELENBP1 mRNA and protein levels were reduced by androgen and elevated by selenium treatment in the normal HOSE cells, whereas reversed responses were observed in the ovarian cancer cell lines. These results suggest that changes of SELENBP1 expression in malignant ovarian cancer are an indicator of aberration of selenium/androgen pathways and may reveal prognostic information of ovarian cancer.
Huang
Kuan-Chun
KC
Laboratory of Gynecologic Oncology, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Brigham and Women's Hospital, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA. khuang@rics.bwh.harvard.edu
Park
Dong Choon
DC
Ng
Shu-Kay
SK
Lee
Ji Young
JY
Ni
Xiaoyan
X
Ng
Wing-Chung
WC
Bandera
Christina A
CA
Welch
William R
WR
Berkowitz
Ross S
RS
Mok
Samuel C
SC
Ng
Shu-Wing
SW
D000368:Aged; D000728:Androgens / Q000502:physiology; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology*; D011379:Prognosis; D020543:Proteome; D012333:RNA, Messenger / Q000096:biosynthesis; D012643:Selenium / Q000494:pharmacology; D051137:Selenium-Binding Proteins / Q000096:biosynthesis* / Q000502:physiology*; D016019:Survival Analysis; D014407:Tumor Cells, Cultured
D000728:Androgens; D020543:Proteome; D012333:RNA, Messenger; C495175:SELENBP1 protein, human; D051137:Selenium-Binding Proteins; D012643:Selenium