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Expression of SOCS3 and Pyk2 and their correlation in non-small cell lung cancer / 中华病理学杂志
Chinese Journal of Pathology ; (12): 657-661, 2012.
Article in Chinese | WPRIM | ID: wpr-303496
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the expression of SOCS3 and Pyk2 and their correlations in non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>The expression of SOCS3 and Pyk2 was detected in 100 cases of NSCLC, human bronchial epithelial cells (HBE) and 6 lung cancer cell lines by immunohistochemistry and immunofluorescence staining. The methylation status of SOCS3 was investigated in A549 cells by methylation-specific PCR. A549 cells were either treated with a demethylation agent 5-aza-2'-deoxycytidine (5-aza) or transfected with three SOCS3 mutants with various functional domains deleted. Besides, the cells were pretreated with a proteasome inhibitor β-lactacystin where indicated. The effects of SOCS3 on Pyk2 expression, Pyk2 Tyr 402 and ERK1/2 phosphorylations were assessed by Western blot. RT-PCR was used to estimate Pyk2 mRNA levels. Transwell experiments were performed to evaluate cell migration.</p><p><b>RESULTS</b>SOCS3 (43.0%, 43/100) and Pyk2 (65.0%, 65/100) were expressed in NSCLC. A significant negative correlation was found between SOCS3 and Pyk2 in both NSCLC tissues and cell lines. SOCS3 was aberrantly methylated and 5-aza restored SOCS3 expression. Transfection studies indicated that exogenous SOCS3 interacted with Pyk2, and both Src homology 2 (SH2) and kinase inhibitory region (KIR) domains contributed to Pyk2 binding. Furthermore, SOCS3 was found to inhibit Pyk2-associated ERK1/2 activity in A549 cells. SOCS3 possibly promoted degradation of Pyk2 in a SOCS-box-dependent manner and interfered with cell migration.</p><p><b>CONCLUSIONS</b>The data indicates that SOCS3 definitely plays roles in regulating Pyk2 signaling, and cell motility. Decreased SOCS3 induced by methylation may confer a migration advantage to A549 cells.</p>
Subject(s)
Full text: Available Index: WPRIM (Western Pacific) Main subject: Pathology / Phosphorylation / Carcinoma, Squamous Cell / Adenocarcinoma / Signal Transduction / Cell Movement / Carcinoma, Non-Small-Cell Lung / DNA Methylation / Cell Line, Tumor / Focal Adhesion Kinase 2 Limits: Humans Language: Chinese Journal: Chinese Journal of Pathology Year: 2012 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Pathology / Phosphorylation / Carcinoma, Squamous Cell / Adenocarcinoma / Signal Transduction / Cell Movement / Carcinoma, Non-Small-Cell Lung / DNA Methylation / Cell Line, Tumor / Focal Adhesion Kinase 2 Limits: Humans Language: Chinese Journal: Chinese Journal of Pathology Year: 2012 Type: Article