103 Recurrent chromosomal deletions status obtained on tissue cores is highly correlated with local invasive and systemic prostate cancer growth

Abstract

INTRODUCTION AND OBJECTIVES: High expression of cysteine-rich 61 (Cyr61) has been associated with a malignant cell phenotype and poor outcome in prostate cancer. The aim of this study is to elucidate the condition around Cyr61 expression and investigate the effect of inhibiting Cyr61 expression using small interfering RNA (siRNA) on the proliferation, migration and invasion. METHODS: RNA interference of Cyr61 was performed using a Cyr61-specific siRNA duplex. Cell proliferation was measured by XTT assay. Apoptosis assay, colony formation assay, wound healing assay and Matrigel invasion assay were examined. RESULTS: Extracellular acidification induced Cyr61 expression in androgen-independent PC-3 cells. Silencing of Cyr61 by siRNA inhibited cell proliferation with enhanced activity of caspase-3/7, upregulation of the proapoptotic Bok, BimL and BimS, cleavage of apoptosis hallmarkers such as Bax, PARP and caspase-3, and downregulation of antiapoptotic Bcl2, Bcl-xL and Mcl-1 proteins. siRNA-based silencing of Cyr61 resulted in the decrease of colonyformation capacity, migration and invasion. At the same time, Cyr61 silencing effectively reduced the levels of phosphorylated Akt and integrin-b3. CONCLUSIONS: Our data indicate that PC-3 cells overproduce Cyr61 as a part of the survival mechanisms under the conditions causing extracellular acidity. Cyr61 modulates integrin-b3 level as well as PI3-kinase/Akt activity through which Cyr61 may mediate tumorigenesis and metastasis. It also suggest the potential importance of Cyr61 targeting on enhancing the therapeutic efficacy of prostate cancer.