低調控proline-rich tyrosine kinase (Pyk2)在非小細胞肺癌細胞的表現將降低腫瘤的惡化性

Abstract

本研究針對腫瘤惡化必經的生理過程：細胞增生、細胞遷移以及血管新生，利用生資工具 Gene Ontology分析找出能夠正調控這三種過程的候選基因─proline-rich tyrosine kinase II (pyk2)。Pyk2是一種focal adhesion tyrosine kinase，在不同的刺激下像是細胞內鈣離子濃度的變化、細胞激素的刺激…等，會分別調控細胞的增生、移動並與血管新生有關。在本研究中利用RNA干擾的技術抑制該基因的表現來探討pyk2在癌症細胞中所扮演的角色。本研究結果顯示，當pyk2的表現受到低調控之時，能夠有效地抑制肺癌細胞A549的生存、增生、遷移以及促進血管新生的能力。因此初步認為pyk2的表現與腫瘤的惡化有關，在未來或許可以針對該目標基因pyk2來進行癌症治療。

The bioinformatics tool, the Gene Ontology analysis proposed proline-rich tyrosine kinase II (pyk2) as a candidate gene for tumor malignancy. pyk2, a second member of the focal adhesion tyrosine kinase-families, which is uniquely situated to act as a critical mediator for the activations of signaling pathways that regulate cell migration, proliferation, survival and angiogenesis. In this study, we down-regulated pyk2 expression of human lung cancer cells, A549, using small interfering RNA (siRNA)-expressing plasmids, and the transfectants were further investigated to examined its effects. Compared to non-treated or control siRNA-transfected cells, the results showed that inhibition of pyk2 expression suppressed survival, proliferation and migration ability of A549 cells.Therefore, Pyk2 might be associated with tumor malignancy and be a potential therapeutic target in cancer treatment.