%0 Journal Article
%T VHZ is a novel centrosomal phosphatase associated with cell growth and human primary cancers
%A Jing Tang
%A Cheng Tan
%A Jie Li
%A Md Monowarul Siddique
%A Ke Guo
%A Siew Chan
%A Jung Park
%A Wan Tay
%A Zhi Huang
%A Wen Li
%A Jian Chen
%A Qi Zeng
%J Molecular Cancer
%D 2010
%I BioMed Central
%R 10.1186/1476-4598-9-128
%X 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.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.Aberrant protein tyrosine phosphorylation can result from the dysregulated expression of protein tyrosine kinases (PTKs) or protein tyrosine phosphatases (PTPs) [1]. Protein phosphorylation and dephosphorylation are major regulatory events in many cellular and pathogenic processes [2]. Considerable attention has centered on protein kinases in cancer development, however the role of protein phosphatases in canc
%U http://www.molecular-cancer.com/content/9/1/128