RECQL1 DNA repair helicase: a potential therapeutic target and a proliferative marker against ovarian cancer.
OBJECTIVE
This study analyzed the clinicopathological correlation between ovarian cancer (OC) and RECQL1 DNA helicase to assess its therapeutic potential.


METHODS
Surgically resected OC from 118 retrospective cases, for which paraffin blocks and all clinical data were complete, were used in this study. RECQL1 and Ki-67 immunostaining were performed on sections to correlate RECQL1 staining with subtype and patient survival. Ten OC and two normal cell lines were then examined for RECQL1 expression and were treated with siRNA against RECQL1 to assess its effect on cell proliferation.


RESULTS
Of the 118 cases of adenocarcinoma (50, serous; 26, endometrioid; 21, clear cell; 15, mucinous; 6, other histology), 104 (90%) showed varying levels of RECQL1 expression in the nuclei of OC cells. The Cox hazards model confirmed that diffuse and strong staining of RECQL1 was correlated with histological type. However, RECQL1 expression did not correlate with overall patient survival or FIGO stage. In vitro, RECQL1 expression was exceptionally high in rapidly growing OC cell lines, as compared with normal cells. Using a time-course analysis of RECQL1-siRNA transfection, we observed a significant inhibition in cell proliferation.


CONCLUSIONS
RECQL1 DNA helicase is a marker of highly proliferative cells. RECQL1-siRNA may offer a new therapeutic strategy against various subtypes of OC, including platinum-resistant cancers, or in recurrent cancers that gain platinum resistance.
Department of Pathology, Kurume University School of Medicine, Fukuoka, Japan. jiro0720@med.kurume-u.ac.jp
Sakiko
S
Sanada
Kazunobu
K
Futami
Atsumu
A
Terada
Koji
K
Yonemoto
Sachiko
S
Ogasawara
Jun
J
Akiba
Makiko
M
Yasumoto
Akiko
A
Sumi
Kimio
K
Ushijima
Toshiharu
T
Kamura
Yasuhiro
Y
Furuichi
Hirohisa
H
Yano
D018262:Adenocarcinoma, Clear Cell / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002288:Adenocarcinoma, Mucinous / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018284:Cystadenocarcinoma, Serous / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D004260:DNA Repair; D005260:Female; D015870:Gene Expression; D006801:Humans; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D053484:RecQ Helicases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D034741:RNA, Small Interfering; D053484:RecQ Helicases