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VHZ is a novel centrosomal phosphatase associated with cell growth and human primary cancers.

ABSTRACT: BACKGROUND: VHZ is a VH1-like (member Z) dual specific protein phosphatase encoded by DUSP23 gene. Some of the dual specific protein phosphatases (DSPs) play an important role in cell cycle control and have shown to be associated with carcinogenesis. Here, the expression of VHZ associated with cell growth and human cancers was investigated. RESULTS: We generated a mouse monoclonal antibody (mAb clone#209) and rabbit polyclonal antibodies (rAb) against VHZ. We performed cell proliferation assay to learn how VHZ is associated with cell cycle by retroviral transduction to express VHZ, VHZ(C95S), and control vector in MCF-7 cells. Overexpression of VHZ [but not VHZ(C95S)] in MCF-7 cells promoted cell proliferation compared to control cells. shRNA-mediated knockdown of VHZ in MCF-7 cells showed that reduction of VHZ resulted in increased G1 but decreased S phase cell populations. Using indirect immunofluorescence, we showed that both exogenous and endogenous VHZ protein was localized at the centrosome in addition to its cytoplasmic distribution. Furthermore, using immunohistochemistry, we revealed that VHZ protein was overexpressed either in enlarged centrosomes (VHZ-centrosomal-stain) of some invasive ductal carcinomas (IDC) Stage I (8/65 cases) or in entire cytoplasm (VHZ-cytosol-stain) of invasive epithelia of some IDC Stage II/III (11/47 cases) of breast cancers examined. More importantly, upregulation of VHZ protein is also associated with numerous types of human cancer, in particular breast cancer. VHZ mAb may be useful as a reagent in clinical diagnosis for assessing VHZ positive tumors. CONCLUSIONS: We generated a VHZ-specific mAb to reveal that VHZ has a novel subcellular localization, namely the centrosome. VHZ is able to facilitate G1/S cell cycle transition in a PTP activity-dependent manner. The upregulation of its protein levels in primary human cancers supports the clinical relevance of the protein in cancers.

SUBMITTER: Tang JP

PROVIDER: S-EPMC2893100 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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VHZ is a novel centrosomal phosphatase associated with cell growth and human primary cancers.

Tang Jing Ping JP Tan Cheng Peow CP Li Jie J Siddique Md Monowarul MM Guo Ke K Chan Siew Wee SW Park Jung Eun JE Tay Wan Ngee WN Huang Zhi Yuan ZY Li Wen Cai WC Chen Jian J Zeng Qi Q

Molecular cancer 20100528

<h4>Background</h4>VHZ is a VH1-like (member Z) dual specific protein phosphatase encoded by DUSP23 gene. Some of the dual specific protein phosphatases (DSPs) play an important role in cell cycle control and have shown to be associated with carcinogenesis. Here, the expression of VHZ associated with cell growth and human cancers was investigated.<h4>Results</h4>We generated a mouse monoclonal antibody (mAb clone#209) and rabbit polyclonal antibodies (rAb) against VHZ. We performed cell prolifer ...[more]

PMID: 20509867

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Project description:ImportanceIn the last 4 decades, survival among patients with human papillomavirus (HPV)-associated cancers has improved, while the incidence of these cancers has increased among younger cohorts. Among survivors of HPV-associated cancers, persistent HPV infection may remain a risk factor for preventable HPV-associated second primary cancers (HPV-SPCs).ObjectivesTo investigate the risk of HPV-SPCs among survivors of HPV-associated index cancers and to test the hypothesis that the HPV-SPC risk among these persons has increased over the last 4 decades.Design, setting, and participantsA retrospective cohort study of 9 cancer registries of the Surveillance, Epidemiology, and End Results (SEER) database was conducted to identify patients with HPV-associated (cervical, vaginal, vulvar, oropharyngeal, anal, and penile) cancers diagnosed from January 1, 1973, through December 31, 2014. The dates of analysis were July 1, 2017, to January 31, 2018.Main outcomes and measuresThe HPV-SPC risk was quantified by calculating standard incidence ratios (SIRs) and excess absolute risks (EARs) per 10 000 person-years at risk (PYR). The HPV-SPC risk by time was estimated using Poisson regression.ResultsFrom 113 272 (73 085 female and 40 187 male) survivors of HPV-associated cancers, 1397 women and 1098 men developed HPV-SPCs. The SIRs for HPV-SPCs were 6.2 (95% CI, 5.9-6.6) among women and 15.8 (95% CI, 14.9-16.8) among men. The EARs were 18.2 per 10 000 PYR for women and 53.5 per 10 000 PYR for men. Among both women and men, those who had index oropharyngeal cancers had the highest HPV-SPC risk (SIR, 19.8 [95% CI, 18.4-21.4] and EAR, 80.6 per 10 000 PYR among women; SIR, 18.0 [95% CI, 16.9-19.1] and EAR, 61.5 per 10 000 PYR among men). Women who had index cervical cancers and men who had index anal cancers had the lowest HPV-SPC risk (SIR, 2.4 [95% CI, 2.2-2.7] and EAR, 4.5 per 10 000 PYR among women; SIR, 6.5 [95% CI, 4.7-8.8] and EAR, 18.5 per 10 000 PYR among men). Both women and men who had index HPV-associated cancers of any kind had a significantly higher risk of oropharyngeal HPV-SPCs. Over the last 4 decades, the risk of developing most types of HPV-SPCs after index cervical, vaginal, and vulvar cancers increased.Conclusions and relevanceAccording to this study, the HPV-SPC risk among survivors of HPV-associated cancers is significant, implying that persistent HPV infection at multiple sites may be associated with HPV-SPCs. These findings have the potential to inform surveillance recommendations for survivors of HPV-associated cancers.

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VHZ is a novel centrosomal phosphatase associated with cell growth and human primary cancers.

Publications

VHZ is a novel centrosomal phosphatase associated with cell growth and human primary cancers.

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