Abstract 2821: Tousled like Kinase 1 binds to and regulates the protein kinase Nek1: Its implication in prostate cancer (original) (raw)

Cancer Research, 2018

Abstract

Introduction: Prostate Cancer (PCa) is one of the most common urological malignancies in men in the United States. Tousled Like kinases (TLKs) are involved in numerous cellular functions, including the DNA Damage Response (DDR). Through a novel proteomic approach, we have identified that NIMA kinase NEK1 strongly interacts and co-localizes with TLKs and has a role in the DDR, upstream of ATR and Chk1. In the present study we have tested Thioridazine (THD), an anti-psychotic drug and inhibitor of TLKs in inhibiting the activity of NEK1 in prostate cancer cell lines and LNCaP cell derived xenografts in NOD/SCID mice and the subsequent role of ATR-Chk1 axis following DNA damage. Material & Methods: We have used a prostate cancer cell line viz. LNCaP, C4-2, C4-2b, 22Rv1, DU145 and PC3 and normal prostate cell line RWPE-1. Clonogenic activity was measured by colony formation assay. Immunoblotting was done for TLKs, NEK1, p-ATR and p-Chk1 protein in PCa cell line and tumor xenografts tiss...

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