RecQL1 DNA Repair Helicase: A Potential Therapeutic Target and Proliferative Marker Against Ovarian Cancer
Sakiko Sanada, Kazunobu Futami, Sachiko Ogasawara, Jun Akiba, Makiko Yasumoto, Kimio Ushijima, Toshiharu Kamura, Yasuhiro Furuichi, Hirohisa Yano. Kurume University School of Medicine, Kurume, Fukuoka, Japan; Genecare Research Institute Co., Ltd., Kamakura, Kanagawa, Japan
Background: RecQL1 helicase belongs to the RecQ DNA helicase family which participates in the maintenance of genomic integrity. RecQL1 is also highly up-regulated in rapidly proliferating cells, including various cancers such as liver, lung, pancreas, head & neck and colon. Silencing RecQL1 in cancer cells by RNA interference with siRNA induces mitotic catastrophe and death in a wide range of cancer cells that have defects in the cell cycle checkpoint system. However in ovarian cancer (OC), the role of RecQL1 has not been studied.
Design: 1) RecQL1 expression and cell growth were examined in 4 OC (e.g., serous and clear cell types) cell lines with or without RecQL1-siRNA transfection. 2) Immunohistochemistry for RecQL1 and Ki-67 were performed on 118 cases of surgically resected OC, i.e., 50 of serous, 26 of endometrioid, 21 of clear cell, 15 of mucinous, and 6 of others. The relationship among RecQL1 and Ki-67 expressions, and clinicopathological parameters was investigated.
Results: 1) Both cell lines showed strong RecQL1 expression. When they treated with RecQL1-siRNA, reduced levels of RecQL1 and various degrees of cell death were observed. 2) The expression of RecQL1 was seen in 90% of the all cases, including 47% of strong (diffuse and intense) RecQL1 expression cases. The strong expression was significantly more frequent in serous type OC (p=0.03), and in OC cases with high Ki-67 expression (p=0.02) and high FIGO stage, although the latter lost value when adjusted by histologic type.
Conclusions: RecQL1 is often expressed in OC and the expression level correlated with proliferative activity. Also it would be an excellent molecular target for OC therapy.
Category: Gynecologic & Obstetrics
Wednesday, March 21, 2012 1:00 PM
Poster Session VI # 209, Wednesday Afternoon