BackgroundThe pre-leukemia transcription factor 3 (PBX) is part of the PBX family of transcription factors, which is known to regulate genes involved in differentiation of urogenital organs and steroidogenesis. This is of interest with regard to prostate cancer progression as regulation of steroidogenesis is one of the mechanisms involved in the development of castration-resistant prostate cancer. In light of this we wanted to investigate the possible involvement of androgen regulation of PBX3 expression in prostate cancer.ResultsIn this study, we show that PBX3 is post-transcriptionally regulated by androgen in prostate cancer cells and that the effect might be independent of the androgen receptor. Furthermore, PBX3 was identified as a target of Let-7d, an androgen regulated microRNA. Let-7d was down-regulated in malignant compared to benign prostate tissue, whereas up-regulation of PBX3 expression was observed.ConclusionsWe demonstrate that PBX3 is up-regulated in prostate cancer and post- transcriptionally regulated by androgen through Let-7d.

Biliary adenofibroma is a rare benign liver tumor with potential for malignant transition. It has a bile duct origin characterized by a complex tubulocystic biliary epithelium with fibrous stroma. MRI features may suggest this uncommon entity, and histological findings can be diagnostic. We report a case of biliary adenofibroma with transformation to an intrahepatic cholangiocarcinoma.

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The main purpose of our project is to determine the role of Pre-B Cell Leukemia Transcription Factor 1 (PBX1) in prostate cancer development and progression. In this study of PBX1, we used immunohistochemical staining of benign and malignant prostate tissue as well as immunoblotting and Real-Time RT-PCR of different prostate cancer cell lines to characterize the expression pattern and regulation of PBX1. Furthermore, we transfected LNCaP with short interference RNA (siRNA) against PBX1 to determine its role in proliferation and differentiation of prostate cancer cells. Our analyses of PBX1 expression in prostate cancer cell lines indicate that the level of PBX1 is higher in LNCaP and VCaP compared to LNCaP C4-2B and DU145, at both the mRNA and protein levels. Immunohistochemical analysis of PBX1 showed that the protein is mainly expressed in basal cells of benign tissue and in a minor sub-fraction of cells located in the luminal compartment. Tumor tissue lacks basal cells and the expression level of PBX1 was therefore down-regulated in malignant compared to benign tissue. In less differentiated tumor areas, the frequency of PBX1 positive cells was lower than in highly differentiated tumors. Thus, an inverse correlation between PBX1 staining and Gleason grade was observed. The TMAstudy included 42 patients radically operated for prostate cancer in 2004 (108 spots) and no significant correlations between PBX1 expression and clinical parameters were observed. Cyclic AMP has previously been shown to induce growth arrest and neurite outgrowth of prostate cancer cells. We have shown that the level of PBX1 mRNA is down-regulated by cAMP. Transient transfection of PBX1 siRNA in LNCaP cells mimicked the morphological changes observed when LNCaP cells are stimulated with cAMP (forskolin) and both treatments reduced the growth rate of LNCaP cells. Several cell cycle regulated genes have been identified as cAMP target genes in LNCaP cells and we are currently investigating whether these are PBX target genes. Furthermore, preliminary studies indicate decreased expression of luminal differentiation markers in LNCaP cells transfected with PBX1 siRNA. Based on these preliminary studies, we suggest that PBX1 might play a role in regulation of development and/or progression of prostate cancer, as suggested for other types of cancers, like ovarian and renal cancers. Citation Format: Hakon Ramberg, Ayham Alshbib, Viktor Berge, Wang Wanzhong, Aud Svindland, Kristin Austlid Taskén. Characterization of pre-B-cell leukemia transcription factor 1 in prostate cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr A49.