Hypoxia and Centrosome Number Alterations in Prostate Cancer

Abstract

Cancer is one of the most prevalent diseases in the world despite the development and abundance of therapies in the last several decades. Prostate cancer is the second leading cause of death due to cancer in males after lung cancer in the United States. Prostate cancer ranked first in the list of estimated new cases and third in estimated deaths in patients with cancer, according to a study by the American Cancer Society. There is a 1 in 8 chance of any male developing prostate cancer in his life span. Most of the cancers show signature mutations in oncogenes and tumor suppressor genes. This is not the case with Prostate Cancer (PCa). Instead it displays large scale genomic instability. This genomic instability includes copy number variations, genetic alterations, aneuploidy, chromothripsis and various other forms of chromosomal instability (CIN). Although, the pathway that leads to this genomic instability in prostate cancer remains unclear, previous studies show that centrosome loss in normal prostate epithelial cells leads to an unstable genome and malignant prostate tumors in xenograft models. Furthermore, some studies have also shown that few cancer cell lines like LnCAP and VCAP also display centrosome loss. It is important to study the centrosome loss in cancer as centrosomes function as major microtubule organising centers of the cell. Acentrososmal spindles can cause segregation errors, lagging chromatids, aneuploidy, polyploidy and micronuclei. Localized prostate tumors have been known to display significant centrosome loss with PCa progression. Understanding the mechanisms that regulate centrosome number and the effect of loss of centrosomes on cancer development may lead to improving current diagnosis and treatments. Thus, we propose to use immortalized prostate epithelial cell line for this study.