TY - JOUR T1 - BRCA1 is Expressed in Uterine Serous Carcinoma (USC) and Controls Insulin-Like Growth Factor I Receptor (IGF-IR) Gene Expression in USC Cell Lines JF - International Journal of Gynecologic Cancer JO - Int J Gynecol Cancer SP - 748 LP - 754 DO - 10.1097/IGC.0b013e318254011f VL - 22 IS - 5 AU - Keren Amichay AU - Debora Kidron AU - Zohar Attias-Geva AU - Hagit Schayek AU - Rive Sarfstein AU - Ami Fishman AU - Haim Werner AU - Ilan Bruchim Y1 - 2012/06/01 UR - http://ijgc.bmj.com/content/22/5/748.abstract N2 - Objective The insulin-like growth factor I receptor (IGF-IR) and BRCA1 affect cell growth and apoptosis. Little information is available about BRCA1 activity on the IGF signaling pathway. This study evaluated the effect of BRCA1 on IGF-IR expression.Methods BRCA1 and IGF-IR immunohistochemistry on archival tissues (35 uterine serous carcinomas [USCs] and 17 metastases) were performed. USPC1 and USPC2 cell lines were transiently cotransfected with an IGF-IR promoter construct driving a luciferase reporter gene and a BRCA1 expression plasmid. Endogenous IGF-IR levels were evaluated by Western immunoblotting.Results We found high BRCA1 and IGF-IR protein expression in primary and metastatic USC tumors. All samples were immunostained for BRCA1—71% strongly stained; and 33/35 (94%) were stained positive for IGF-IR—2 (6%) strongly stained. No difference in BRCA1 and IGF-IR staining intensity was noted between BRCA1/2 mutation carriers and noncarriers. Metastatic tumors stained more intensely for BRCA1 than did the primary tumor site (P = 0.041) and with borderline significance for IGF-IR (P = 0.069). BRCA1 and IGF-IR staining did not correlate to survival. BRCA1 expression led to 35% and 54% reduction in IGF-IR promoter activity in the USPC1 and USCP2 cell lines, respectively. Western immunoblotting showed a decline in phosphorylated IGF-IR and phosphorylated AKT in both transiently and stably transfected cells.Conclusions BRCA1 and IGF-IR are highly expressed in USC tumors. BRCA1 suppresses IGF-IR gene expression and activity. These findings suggest a possible biological link between the BRCA1 and the IGF-I signaling pathways in USC. The clinical implications of this association need to be explored. ER -