Abstract 2167: Identification of aberrant expression of HOXA10 in prostate cancer
Authors: Marco A. De Velasco, Erina Okazaki, Yi Wang, Ayaka Izumi, Yuji Hatanaka, Motoyoshi Tanaka, Charles Rosser, Steve Goodison, Nobutaka Shimizu, Kazuhiro Yoshimura, Masahiro Nozawa, Kazuhiro Yoshikawa, Kazuto Nishio, Hirotugu Uemura
Journal: Cancer Research (2011)

Abstract Background: Prostate cancer progression follows a series of defined states, which include prostatic intraepithelial neoplasia (PIN), prostate adenocarcinoma in situ, locally invasive adenocarcinoma and eventually metastatic cancer. One pathway with a prominent role in prostate cancer is the PI3K/Akt/mTOR pathway. Current estimates suggest that PI3K/Akt/mTOR signaling is upregulated in 30-50% of prostate cancers, often through loss of PTEN. In order to identify novel genes potentially regulated by Pten in prostate cancer cells, we performed a comprehensive genome-wide microarray analysis of genes differentially up- or down-regulated in PSACre;PtenloxP/loxP mutant mice. Methods: Total RNAs were collected form the prostate glands of tumor bearing PSACre;PtenloxP/loxP mutant and wild type mice. cDNAs were generated and were then hybridized onto Affymetrix microarray chips and analyzed with Agilent's Gene Spring software. Differentially expressed genes were analyzed and candidate genes were selected and validated by qRT-PCR. Protein expression levels in mouse prostates were analyzed using western blot and immunohistochemical methods. Protein expression levels in human tissues were determined by immunohistochemical methods in archived formalin fixed paraffin embedded tissues. Results: Microarray analysis revealed that HOXA10 was significantly downregulated in Pten mutant mice compared to wildtype controls. qRT-PCR results from mice at different stage of tumor development revealed a different pattern of expression. HOXA10 is a member of the homeobox gene family and is a transcription factors primarily involved in embryonic development. Therefore, we examined the expression of HOXA10 at the protein level by immunohistochemical staining of mouse prostate cancer ranging from normal to highly metastatic cancer. Or observations revealed that expression is high in normal and hyperplastic glands and gradually decreases as tumor grade increases. However, HOXA10 expression rose focally in poorly differentiated tumors and was highly expressed in metastatic tumors. We examined the expression patterns of HOXA10 in 10 cases of human prostate cancer and benign prostatic hyperplasia. As in mice, expression was high in normal and benign glands; moderate in Gleason score 6; low in Gleason score 7-8; low with nest of moderate to strong stained cells in Gleason score 9; and high in metastasis. Immunohistochemical hierarchical cluster analysis showed an inverse pattern of expression between HOXA10 and vimentin. Conclusion: Our results have shown that HOXA10 is aberrantly expressed in both human and mouse prostate cancer and appears to be involved in the carcinogenesis process, particularly in the development of metastasis. Further work is currently ongoing to elucidate the role HOXA10 plays in prostate cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2167. doi:10.1158/1538-7445.AM2011-2167