title: Vav3 oncogene is involved in regulation of secretory phospholipase A2-IIa expression in prostate cancer.
abstract: Our previous study revealed that Vav3 oncogene and secretory phospholipase A2-IIa (sPLA2-IIa) are overexpressed in androgen-independent prostate cancer cells relative to their androgen-dependent counterparts and contribute to development of hormone refractory prostate cancer. Vav3 is a multiple function protein with both signaling molecule and coactivator activities. sPLA2-IIa is a downstream effector of HER/HER2-PI3K-Akt-NF-κB signaling and involved in inflammatory response and tumorigenesis. The aim of the current study was to determine whether Vav3 is involved in up-regulation of sPLA2-IIa expression, given that Vav3 signals in the HER/HER2-elicited pathway. Among 46 prostate cancer specimens examined, Vav3 and sPLA2-IIa are overexpressed in 48 and 83% human prostate cancers, respectively. Vav3 overexpression is significantly associated with a high level expression of sPLA2-IIa. In addition, significant Vav3 nuclear localization is observed in two prostate cancer specimens, supporting a coactivator activity in prostate cancer cells. Further analysis revealed that Vav3 up-regulates expression of the sPLA2-IIa gene at the transcriptional level via HER/HER2-PI3K-Akt-NF-κB signaling. These data revealed that Vav3 overexpression as an additional underlying mechanism contributes to elevated sPLA2-IIa expression in prostate cancer.
authors: Department of Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
authors: Zhongyun
authors: Z
authors: Dong
authors: Yin
authors: Y
authors: Liu
authors: Linda
authors: L
authors: Levin
authors: Leslie
authors: L
authors: Oleksowicz
authors: Jiang
authors: J
authors: Wang
authors: Shan
authors: S
authors: Lu
mesh_terms: D015870:Gene Expression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D054501:Group II Phospholipases A2 / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D051567:Proto-Oncogene Proteins c-vav / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
chemical_list: D051567:Proto-Oncogene Proteins c-vav; C496621:VAV3 protein, human; D054501:Group II Phospholipases A2; C516287:PLA2G2A protein, human