Join us for full day of mesothelioma patient education next Friday, September 26. Our research and clinical experts from Penn’s Mesothelioma and Pleural Program, with support from the Mesothelioma Applied Research Foundation, will give the latest in mesothelioma treatment and care for those at risk or diagnosed with mesothelioma.

Who should attend?

When, where and what?

Date: Friday, September 26, 2014
Time: 10 a.m. to 3 p.m.
Location: The Hub, Cira Center, 2929 Arch Street, Philadelphia, PA 19104

The full event agenda includes:

• Q&As with Penn and MARF experts
• Information on new clinical trials for mesothelioma
• The latest in new treatment options for both peritoneal and pleural mesothelioma
• An overview of palliative care options
• Early detection and risk factor assessment
• The future of mesothelioma on a genetic level

Join us for full day of mesothelioma patient education next Friday, September 26. Our research and clinical experts from Penn’s Mesothelioma and Pleural Program, with support from the Mesothelioma Applied Research Foundation, will give the latest in mesothelioma treatment and care for those at risk or diagnosed with mesothelioma.

Who should attend?

When, where and what?

Date: Friday, September 26, 2014
Time: 10 a.m. to 3 p.m.
Location: The Hub, Cira Center, 2929 Arch Street, Philadelphia, PA 19104

The full event agenda includes:

• Q&As with Penn and MARF experts
• Information on new clinical trials for mesothelioma
• The latest in new treatment options for both peritoneal and pleural mesothelioma
• An overview of palliative care options
• Early detection and risk factor assessment
• The future of mesothelioma on a genetic level

The androgen receptor (AR) is the key driver of both early and advanced prostate cancer, making a complete understanding of its regulation important. Here, we report the identification of multiple AR-binding sites in the gene encoding the transcription factor CtBP2 (carboxyl terminal–binding protein), genetic variations of which have been associated with prostate cancer susceptibility. Notably, we found that SNPs in the human CTBP2 gene that were associated with prostate cancer development were correlated with AR-enhancer activity. High CtBP2 expression levels correlated with poor prognosis in patients, whereas CtBP2 silencing reduced tumor growth in a mouse xenograft model of human prostate cancer. Consistent with its function as a transcriptional corepressor, CtBP2 repressed tumor-suppressor genes and AR corepressors in prostate cancer cells, such as NCOR and RIP140, by binding with AR to the promoter enhancers of these genes. Global gene-expression analyses revealed a positive effect on androgen-mediated gene expression, and CtBP2 silencing was found to increase AR interactions with corepressors that limit histone modification. Overall, our results show how CtBP2 contributes to prostate cancer progression by modulating AR and oncogenic signaling. Cancer Res; 74(22); 1–12. ©2014 AACR.

The androgen receptor (AR) is the key driver of both early and advanced prostate cancer (PCa), making a complete understanding of its regulation important. Here we report the identification of multiple AR binding sites in the gene encoding the transcription factor CtBP2, genetic variations of which have been associated to PCa susceptibility. Notably, we found that single-nucleotide polymorphisms in the human CTBP2 gene that were associated with PCa development were correlated with AR enhancer activity. High CtBP2 expression levels correlated with poor prognosis in patients, whereas CtBP2 silencing reduced tumor growth in a mouse xenograft model of human PCa. Consistent with its function as a transcriptional co-repressor, CtBP2 repressed tumor suppressor genes and AR co-repressors in PCa cells, such as NCOR and RIP140, by binding with AR to the promoter-enhancers of these genes. Global gene expression analyses revealed a positive effect on androgen-mediated gene expression, and CtBP2 silencing was found to increase AR interactions with co-repressors that limit histone modification. Overall, our results show how CtBP2 contributes to prostate cancer progression by modulating AR and oncogenic signaling.

Microtubule nucleation requires the γ-tubulin ring complex, and during the M-phase (mitosis) this complex accumulates at the centrosome to support mitotic spindle formation. The posttranslational modification of γ-tubulin through ubiquitination is vital for regulating microtubule nucleation and centrosome duplication. Blocking the BRCA1/BARD1-dependent ubiquitination of γ-tubulin causes centrosome amplification. In the current study, we identified BRCA1-associated protein-1 (BAP1) as a deubiquitination enzyme for γ-tubulin. BAP1 was downregulated in metastatic adenocarcinoma breast cell lines compared with noncancerous human breast epithelial cells. Furthermore, low expression of BAP1 was associated with reduced overall survival of patients with breast cancer. Reduced expression of BAP1 in breast cancer cell lines was associated with mitotic abnormalities. Importantly, rescue experiments including expression of full length but not the catalytic mutant of BAP1 reduced ubiquitination of γ-tubulin and prevented mitotic defects. Our study uncovers a new mechanism for BAP1 involved in deubiquitination of γ-tubulin, which is required to prevent abnormal mitotic spindle formation and genome instability. Cancer Res; 74(22); 1–10. ©2014 AACR.