Browsing by Author "Zaaluk, Hend"

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    ARPC1B Gene: As a Potential Novel Prostate Cancer Driver
    (2019-12) Zaaluk, Hend; Bismar, Tarek A.; Riabowol, Karl T.; Argiropoulos, Bob; Lees-Miller, Susan; Eszlinger, Markus
    Prostate cancer is the most common malignancy in men and the second leading cause of cancer-related deaths in western countries. Currently, there is a lack of specific molecular markers that can predict cancer progression and prognosis. Characterization of prostate cancer driver genes is essential for investigating the cellular changes that influence the progression of cancer. This will provide a better understanding to prostate cancer carcinogenesis, elucidate novel biomarkers, and improve clinical outcomes. Previously our lab performed a bioinformatics screen using several public cohorts and identified a panel of genes that are deregulated on the mRNA and DNA levels. We hypothesize that these gene are potentially acting as oncogenes and tumor suppressors that could be related to the prognosis of prostate cancer. Actin-related protein -2/3 subunit B (ARPC1B) was found to be one of the most highly dysregulated genes. Dysregulation of ARPC1B expression has been detected in multiple human cancers and ARPC1B protein has been implicated in the control of actin polymerization. Moreover, ARPC1B is involved in many pathways such as cytoskeleton remodeling via actin; integrin mediated cell adhesion and movement of cell/subcellular compartments. The purpose of this research was to evaluate the expression levels of ARPC1B in different prostate cancer cell lines and investigate its potential role in disease progression. ARPC1B expression was analysed using western blot and qRT-PCR in multiple cell lines. We found ARPC1B protein and mRNA levels to be upregulated in the PC3 cell line compared to other cell lines. To validate the role of ARPC1B, siRNA was used to knockdown ARPC1B in PC3 cells which resulted in significant reduction of cell proliferation as measured using the MTS assay. Reduced cell growth and/or reduced migration in cells with ARPC1b knocked down was also seen using scratch assays. Tissue expression levels were also investigated on a progression tissue microarray and showed increased intensity with disease progression from benign to localized cancer and castrate resistant disease. These data suggest that ARPC1B could be a valid prostate cancer marker.