Abstract 5565: Differential changes of proteome profiles in the dorsal-lateral vs. ventral prostate of during TRAMP carcinogenesis

Abstract

Abstract The transgenic adenocarcinoma of mouse prostate (TRAMP) model is being widely used in the field of prostate cancer chemoprevention. As is understood today, the TRAMP represents at least two models of prostate carcinogenesis in the dorsal-lateral prostate (DLP, epithelial) and ventral prostate (VP, neuroendocrine). However, the molecular basis for the two lobe-specific lineages of carcinogenesis is poorly defined. To this end, we profiled concurrently the proteomes of DLP and VP lobes from the prostate of both TRAMP and wild type littermate C57BL/6 mice at the age of 17-18 weeks by 2D LC-MALDI-TOF/TOF with iTRAQ labeling. Totally 748 proteins were identified. In wild-type mice, 84 proteins were found to have different expression levels (cut-off 20%) between DLP and VP, including experimental autoimmune prostatitis antigen 2 (EAPA2), beta-tropomyosin, heat shock protein 5 (GRP78) and clusterin. In TRAMP mice, 118 proteins were found to be significantly changed in DLP and/or VP during TRAMP carcinogenesis. Among these 118 proteins, 55 and 36 proteins were uniquely changed in DLP or VP lobe, respectively, and 27 proteins in both DLP and LP lobe. 24 of the 27 proteins shared the same trend, albeit the extent of change was not exactly the same. Those shared changes such as up-regulation of HMGB 1&2 and down-regulation of calponin-1 indicated possible common molecular events associated with TRAMP carcinogenesis. The other three proteins, clusterin, polymeric immunoglobulin receptor and aldose reductase went in opposing directions in DLP versus VP during carcinogenesis. Those three proteins, as well as other proteins changed only in DLP or VP (e.g. EAPA2 in DLP and alpha-2-macroglobulin in VP), are more likely related to lobe-specific mechanisms of carcinogenesis. The lobe-specific and TRAMP-related expression patterns of GRP78 and clusterin were further validated by western blot. Ingenuity Pathway Analysis identified 14-3-3 zeta/delta (up-regulated only in DLP), epidermal growth factor (EGF, up-regulated only in DLP) and NF-κB as distinct inferred network nodes in TRAMP carcinogenesis in DLP lobe, whereas ERK1/2 and FGF2 were recognized as network nodes in VP lobe during carcinogenesis. Additional experiments confirmed lobe-specific expression patterns of NF-κB p65 and FGF2 in both wild type and TRAMP mice. Overall our data-sets highlight different mechanisms were likely involved in modifying carcinogenesis in DLP and VP. 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 5565. doi:10.1158/1538-7445.AM2011-5565