Abstract. Clinically high-grade prostate cancers (PC) with high Gleason scores of 8-10 exhibit rapid growth and are more likely to spread beyond the prostate. These cancer types demonstrate a poor response to androgen deprivation therapy and eventually acquire a castration-resistant phenotype. To identify novel molecular cancer drug targets, we previously analyzed the gene expression profiles of high-grade PC using a cDNA microarray combined with laser microbeam microdissection and found a number of genes that are transactivated in high-grade PC. Among these genes, we report the identification of a novel molecular target, small nuclear ribonucleoprotein polypeptide E (SNRPE). Semi-quantitative RT-PCR confirmed that SNRPE is overexpressed in high-grade PC cells compared with normal prostatic epithelial cells. Knockdown of SNRPE expression by short interfering RNA (siRNA) resulted in the marked suppression of PC cell proliferation. By contrast, SNRPE overexpression promoted PC cell proliferation, indicating its oncogenic effects. Furthermore, we demonstrated that SNRPE regulates androgen receptor (AR) mRNA expression in PC cells. Knockdown of SNRPE expression by siRNA resulted in the marked suppression of AR and its downstream target genes at the mRNA level. We suggest that the regulation of AR expression by SNRPE is essential for cell proliferation and progression of high-grade PC and that it may be a novel molecular target for cancer drugs.

Prostate cancer (PC) is usually androgen-dependent and responds well to androgen ablation therapy. However, at a certain stage some prostate cancers eventually acquire a castration-resistant phenotype. These cancer cells are originally high-grade and show very poor response to any anticancer therapies. To identify novel molecular cancer drug targets, we previously analyzed the gene expression profiles of high-grade PCs using a cDNA microarray combined with laser microbeam microdissection and found a number of genes that are transactivated in high-grade PC. Among them, we report the identification of a novel molecular target, SHISA2. We confirmed overexpression of SHISA2 in high-grade prostate cancer cells by semi-quantitative RT-PCR and immunohistochemical analysis. Knockdown of SHISA2 expression by siRNA in a prostate cancer cell line resulted in a drastic decrease of cell numbers. In contrast, SHISA2 overexpression in a prostate cancer cell line promoted cell proliferation. These findings suggest that SHISA2 could be involved in aggressive phenotype of prostate cancers, including castration-resistant prostate cancers, and that it should be a potential molecular target for development of new therapeutics and a diagnostic biomarker for aggressive prostate cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1849. doi:1538-7445.AM2012-1849

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Clinically high-grade prostate cancers (PC) with high Gleason scores of 8-10 tend to grow quickly and are more likely to spread beyond the prostate. They show a poor response to androgen deprivation therapy and eventually acquire a castration-resistant phenotype. To identify novel molecular cancer drug targets, we previously analyzed the gene expression profiles of high-grade PC using a cDNA microarray combined with laser microbeam microdissection and found a number of genes that are transactivated in high-grade PC. Among them, we report the identification of a novel molecular target, small nuclear ribonucleoprotein polypeptide E (SNRPE). Semi-quantitative RT-PCR confirmed that SNRPE is overexpressed in high-grade PC cells compared with normal prostatic epithelial cells (NP). Knockdown of SNRPE expression by short interfering RNA (siRNA) resulted in the marked suppression of PC cell proliferation. In contrast, SNRPE overexpression promoted PC cell proliferation, indicating its oncogenic effects. Furthermore, we demonstrated that SNRPE regulates androgen receptor (AR) mRNA expression in PC cells. Knockdown of SNRPE expression by siRNA resulted in the marked suppression of AR and its downstream target genes at the mRNA level. We suggest that the regulation of AR expression by SNRPE is essential for the cell proliferation and progression of high-grade PC and that it could be a novel molecular target for cancer drugs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1847. doi:1538-7445.AM2012-1847

Introduction: Sarcomatoid carcinoma of the urinary bladder is a rare bidirectional malignant neoplasm with epithelial and mesenchymal differentiation. The epithelial component is mainly high-grade urothelial carcinoma, and the mesenchymal component includes rhabdomyosarcoma. However, proper differential diagnosis of adult rhabdomyosarcomatous tumors of the bladder can be a challenge. Moreover, low-grade urothelial carcinoma as the epithelial component of sarcomatoid carcinoma has not been reported. Case presentation: A 64-year-old Asian man with a history of transurethral resection of low-grade urothelial carcinoma of the bladder visited our department with complaints of frequent urination and macroscopic hematuria. Computed tomography and magnetic resonance imaging demonstrated a large mass located in the anterior wall of the bladder. Pathological diagnosis of transurethral biopsy was low-grade, non-invasive papillary urothelial carcinoma, and tumor tissue was removed by total cystectomy. Immunohistochemical studies and fluorescence in situ hybridization assay of the resected neoplastic tissue revealed extensive rhabdomyosarcomatous differentiation causing the formation of a large pedunculated polyp with a papillary appearance of recurrent low-grade urothelial carcinoma. No evidence of recurrence was detected during 2 years of follow-up without further treatment. Conclusions: Urothelial carcinoma of the urinary bladder with extensive rhabdomyosarcomatous differentiation is rare, but it should be considered in the differential diagnosis even when urothelial carcinoma coexisting with a rhabdomyosarcomatous component is low-grade and non-invasive.