Abstract 2837: Differential expression of Protocadherin-7 (PCDH7) in prostate cancer (PCa) cells: a direct association between PCDH7 and castrate resistant PCa

Abstract

Abstract Introduction: PCa is the most commonly diagnosed disease in American men and the second leading cause of death among them. Most of PCa deaths are a result of distant metastasis and due to emergence of castrate resistant PCa. Protocadherin-7 (PCDH7), a Cadherin superfamily transmembrane protein that is known to function in cell-cell recognition and adhesion, is reported to be overexpressed in breast cancer and non-small cell lung cancer (NSCLC). PCDH7 has been shown to mediate brain metastasis of breast cancer. Overexpression of PCDH7 was reported to be associated with poor clinical outcome of NSCLC. However, there is no report on involvement of PCDH7 in PCa tumorigenesis and metastasis. In the present study we evaluated expression of PCDH7 in androgen dependent and androgen independent PCa cells and in TCGA and Trento/Cornell/Broad 2016 clinical data sets. Materials and Methods: PCa cells- LNCaP, C4-2b, DU145, PC3, 22Rv1 and RWPE1 were used in this study. Protein expression was checked by Western Blotting. mRNA levels were checked by quantitative real time PCR. Results: Our data reveal high PCDH7 protein expression in PC3 cells and low levels of PCDH7 in LNCaP and RWPE1 cells. qRT-PCR confirmed an increased transcript level of PCDH7 in PC3 and low levels in LNCaP cells. We also observed elevated transcript levels for PCDH7 in castrate resistant and Enzalutamide refractory PCa (22Rv1) cells. These data suggest a direct relationship between castrate resistance and PCDH7 expression. Our results also show an inverse relationship between PCDH7 and E-Cadherin and a direct relationship between PCDH7 and EMT markers, indicating expression of PCDH7 is associated with tumor progression. Interestingly, there was no correlation between PCDH7 with tumor grade or metastasis from TCGA data, but analysis of NEPC (Trento/Cornell/Broad 2016) data set revealed amplification of PCDH7 in 9% of NEPC tumors. Collectively, these data suggest PCDH7 expression may be associated with advanced PCa in general and NEPC phenotype PCa in particular. Conclusion: Our results suggest direct association of PCDH7 expression and castrate resistance in PCa cell lines. Role of PCDH7 in castrate resistant PCa needs further evaluation. Citation Format: Gauri Shishodia, Sweaty Koul, Qin Dong, Hari K. Koul. Differential expression of Protocadherin-7 (PCDH7) in prostate cancer (PCa) cells: a direct association between PCDH7 and castrate resistant PCa [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2837. doi:10.1158/1538-7445.AM2017-2837