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Expression loss and revivification of RhoB gene in ovary carcinoma carcinogenesis and development.

Liu Y, Song N, Ren K, Meng S, Xie Y, Long Q, Chen X, Zhao X - PLoS ONE (2013)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Gynecology & Obstetrics, West China Second Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.

ABSTRACT
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.

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RhoB gene expression and ovary carcinoma differentiation.RhoB expression levels were analyzed respectively in well-, medium-, and poor-differentiated ovarian cancer using immunohistochemistry staining of individual paraffin sections. RhoB is expressed in the cytoplasm of monolayered ovarian surface epithelial cells for well-differentiated ovary caicinoma (AB); in medium-differentiated tumor, RhoB is expressed in the monolayered and multilayered regions of epithelium tumor (CD); and RhoB is lost in the multilayered region of epithelium for poor-differentiated tumor (EF). (G) It is clear that Poor-differentiated tumors had a significant reduction in the expression of RhoB (80% reduction) than medium differentiated (44% reduction) and well differentiated ovary cancer (28.5% reduction).
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pone-0078417-g002: RhoB gene expression and ovary carcinoma differentiation.RhoB expression levels were analyzed respectively in well-, medium-, and poor-differentiated ovarian cancer using immunohistochemistry staining of individual paraffin sections. RhoB is expressed in the cytoplasm of monolayered ovarian surface epithelial cells for well-differentiated ovary caicinoma (AB); in medium-differentiated tumor, RhoB is expressed in the monolayered and multilayered regions of epithelium tumor (CD); and RhoB is lost in the multilayered region of epithelium for poor-differentiated tumor (EF). (G) It is clear that Poor-differentiated tumors had a significant reduction in the expression of RhoB (80% reduction) than medium differentiated (44% reduction) and well differentiated ovary cancer (28.5% reduction).

Mentions: Out of 57 cases of malignant tumors, RhoB negative expression was detected in 27 cases, and only faint staining was observed in 14 cases. Obviously, the expression of RhoB was obviously reduced or lost in the majority of malignant tumors. No obvious difference was seen between various histological types. It is clear that RhoB expression is detected in normal ovary epithelium, borderline tumors, and decreases significantly in malignant tumors (P<05). Poor differentiated tumors had a greater (80%) reduction in the expression of RhoB than medium differentiated (44% reduction) and well differentiated ovary cancer (28.5% reduction). RhoB is expressed in the cytoplasm of monolayered ovarian surface epithelial cells, and its expression is lost in the multilayered region of epithelium (Figure 2).


Expression loss and revivification of RhoB gene in ovary carcinoma carcinogenesis and development.

Liu Y, Song N, Ren K, Meng S, Xie Y, Long Q, Chen X, Zhao X - PLoS ONE (2013)

RhoB gene expression and ovary carcinoma differentiation.RhoB expression levels were analyzed respectively in well-, medium-, and poor-differentiated ovarian cancer using immunohistochemistry staining of individual paraffin sections. RhoB is expressed in the cytoplasm of monolayered ovarian surface epithelial cells for well-differentiated ovary caicinoma (AB); in medium-differentiated tumor, RhoB is expressed in the monolayered and multilayered regions of epithelium tumor (CD); and RhoB is lost in the multilayered region of epithelium for poor-differentiated tumor (EF). (G) It is clear that Poor-differentiated tumors had a significant reduction in the expression of RhoB (80% reduction) than medium differentiated (44% reduction) and well differentiated ovary cancer (28.5% reduction).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3815309&req=5

pone-0078417-g002: RhoB gene expression and ovary carcinoma differentiation.RhoB expression levels were analyzed respectively in well-, medium-, and poor-differentiated ovarian cancer using immunohistochemistry staining of individual paraffin sections. RhoB is expressed in the cytoplasm of monolayered ovarian surface epithelial cells for well-differentiated ovary caicinoma (AB); in medium-differentiated tumor, RhoB is expressed in the monolayered and multilayered regions of epithelium tumor (CD); and RhoB is lost in the multilayered region of epithelium for poor-differentiated tumor (EF). (G) It is clear that Poor-differentiated tumors had a significant reduction in the expression of RhoB (80% reduction) than medium differentiated (44% reduction) and well differentiated ovary cancer (28.5% reduction).
Mentions: Out of 57 cases of malignant tumors, RhoB negative expression was detected in 27 cases, and only faint staining was observed in 14 cases. Obviously, the expression of RhoB was obviously reduced or lost in the majority of malignant tumors. No obvious difference was seen between various histological types. It is clear that RhoB expression is detected in normal ovary epithelium, borderline tumors, and decreases significantly in malignant tumors (P<05). Poor differentiated tumors had a greater (80%) reduction in the expression of RhoB than medium differentiated (44% reduction) and well differentiated ovary cancer (28.5% reduction). RhoB is expressed in the cytoplasm of monolayered ovarian surface epithelial cells, and its expression is lost in the multilayered region of epithelium (Figure 2).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Gynecology & Obstetrics, West China Second Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus