Expression loss and revivification of RhoB gene in ovary carcinoma carcinogenesis and development.
RhoB, a member of small GTPases belonging to the Ras protein superfamily, might have a suppressive activity in cancer progression. Here, expression of RhoB gene was evaluated in human benign, borderline and malignant ovary tumors by immunostaining, with normal ovary tissue as control. Malignant tumors were assessed according to Federation Internationale de Gynecologie Obstetrique (FIGO) guidelines and classified in stage I-IV. Revivification of RhoB gene was investigated by analyzing the effect of histone deacetylase (HDAC) inhibitor trichostatin (TSA) and methyltransferase inhibitor 5-azacytidine (5-Aza) on ovarian cancer cells via RT-PCR and western blot. Apoptosis of ovary cancer cells was detected using flowcytometry and fluorescence microscopy. Subsequently, RhoB expression is detected in normal ovary epithelium, borderline tumors, and decreases significantly or lost in the majority of ovarian cancer specimen (P<0.05). RhoB expression decreases significantly from stage II (71.4%) to stage III (43.5%) to stage IV (18.2%, P<0.05). TSA can both significantly revive the RhoB gene and mediate apoptosis of ovarian cancer cells, but 5-Aza couldn't. Interference into Revivification of RhoB gene results in reduction of ovary carcinoma cell apoptosis. It is proposed that loss of RhoB expression occurs frequently in ovary carcinogenesis and progression and its expression could be regulated by histone deacetylation but not by promoter hypermethylation, which may serve as a prospective gene treatment target for the patients with ovarian malignancy not responding to standard therapies.
Department of Gynecology & Obstetrics, West China Second Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
Yingwei
Y
Liu
Na
N
Song
Kexing
K
Ren
Shenglan
S
Meng
Yao
Y
Xie
Qida
Q
Long
Xiancheng
X
Chen
Xia
X
Zhao
D000970:Antineoplastic Agents / Q000494:pharmacology; D001374:Azacitidine / Q000494:pharmacology; D063646:Carcinogenesis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D018293:Cystadenoma, Serous / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006655:Histone Deacetylases / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010053:Ovary / Q000378:metabolism / Q000473:pathology; D020743:rhoB GTP-Binding Protein / Q000235:genetics* / Q000378:metabolism
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; C012589:trichostatin A; D008780:Methyltransferases; D006655:Histone Deacetylases; D020743:rhoB GTP-Binding Protein; D001374:Azacitidine