COUP-TFII sparks prostate cancer progression

HOUSTON -- (November 28, 2012) -- Prostate cancer presents a dilemma for patients and the physicians who treat them. Which cancers are essentially indolent and present no risk and which are life threatening? Which can be watched and which need aggressive treatment?

Drs. Ming-Jer and Sophia Tsai, both professors in the department of molecular and cellular biology at Baylor College of Medicine, think a receptor called COUP-TFII that they have long studied may point the way to an answer. In a study that appears online in the journal Nature, they show that high levels (overexpression) of COUP-TFII can overcome a natural barrier to progression of prostate cancer, allowing tumor cells to grow and spread throughout the body – a process called metastasis.

"Levels of COUP-TFII provide a good prognostic marker for prostate cancer when added to other known markers of the disease," said Dr. Ming-Jer Tsai.

"COUP-TFII is an important ‘second hit’ for the progression of prostate cancer and metastasis," said Dr. Sophia Tsai. In other words, one "hit" or mutation might start the process of cells becoming cancerous. The second "hit" would make them more aggressive.

In studies of patient samples, loss of a protein called PTEN or mutations in another signaling pathway called PI3K show up in prostate tumors. However, tumors in which PTEN is lost can remain indolent. One theory is that loss of PTEN increases TGF-beta signaling, which creates a barrier to prostate cancer progression.

The Tsais’ studies in mice that lack PTEN show that loss of COUP-TFII inhibits the development of prostate tumors in the animals. When mice have a gene that produces insufficient levels of PTEN, COUP-TFII overexpression enhances prostate tumor progression. Further studies in mice that lost PTEN showed that high levels of COUP-TFII promoted the metastatic spread of the prostate cancer.

Studies in cell cultures and in human tissues confirmed the activity of COUP-TFII in promoting a more aggressive form of prostate cancer that could spread and metastasize.

The next step is find out how to inhibit COUP-TFII and prevent so-called indolent prostate cancers from becoming more aggressive, said Ming-Jer Tsai.

Others who took part in this work include Jun Qin, San-Pin Wu, Fangyan Dai, Xin Xie, Chiang-Min Cheng, Chad J. Creighton, Anna Frolov, Gustavo Ayala, Xia Lin, Xin-Hua Feng and, Michael M. Ittmann, all of BCM and Shaw-Jenq Tsai of National Cheng Kung University College of Medicine in Tainan, Taiwan. Ayala is now with the University of Texas Medical School at Houston.

Funding for this study came from the National Institutes of Health (NIH DK62434, DK59820, DK45641 and HL76448).

Dr. Sophia Tsai holds the Gordon Cain Professorship and Dr. Ming-Jer Tsai holds the Charles C. Bell, Jr. and Distinguished Service Professorship in Cell Biology.

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For more information on research at Baylor College of Medicine, please go to www.bcm.edu/fromthelab.

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Prostate Cancer and Occupational Whole-Body Vibration Exposure

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Victoria Nadalin1,*, Nancy Kreiger1,2, Marie-Elise Parent3, Alan Salmoni4, Andrea Sass-Kortsak5, Jack Siemiatycki6, Margaret Sloan1 and James Purdham5

1Research, Prevention and Cancer Control, Cancer Care Ontario, 620 University Avenue, Toronto, Ontario, Canada M5G 2L7

2Epidemiology, Dalla Lana School of Public Health, University of Toronto, 155 College Street, Toronto, Ontario, Canada M5T 3M7

3Institut Armand Frappier, Institut National de la Recherche Scientifique, Universite de Quebec, 531, boulevard des Prairies, Laval, Québec, Canada H7V 1B7

4School of Kinesiology, Faculty of Health Sciences, Western University, London, Ontario, Canada N6A 5B9

5Occupational and Environmental Health, Gage Occupational & Environmental Health Unit, 223 College St., Toronto, Ontario, Canada M5T 1R4

6Department of Social and Preventive Medicine, University of Montreal, PO Box 6128, Station Centre-ville, Montréal, Quebec, Canada H3C 3J7 ?* Author to whom correspondence should be addressed. Tel: (416)-971-9800 ext. 3251; fax: (416)-971-7554; e-mail: Victoria.nadalin{at}cancercare.on.ca Received July 6, 2011. Accepted February 3, 2012. Prostate cancer is common and its etiology largely unknown; therefore, it is important to explore all potential risk factors that are biologically plausible. Recent literature suggests a relationship between whole-body vibration (WBV) and prostate cancer risk. The aim of this study was to determine whether occupational WBV was a risk factor for prostate cancer. Existing data, collected on 447 incident cases and 532 population controls (or their proxies), in Montreal, Canada, were used to evaluate this question. Personal interviews collected detailed job descriptions for every job held, the tasks involved, and type of equipment used. For each job, experts assessed the intensity and daily duration of WBV exposure. Inter-rater agreement for WBV ratings was examined using the kappa statistic, with values that ranged from 0.83 to 0.94. Logistic regression models explored the relationship between WBV exposure and prostate cancer, using various combinations of intensity, daily duration, and years of exposure. Potential confounders were also examined. Occupations with WBV exposure demonstrated an increased statistically non-significant risk [odds ratio (OR) = 1.44, 95% confidence interval (CI): 0.99–2.09]. The risk for transport equipment operation, a job with WBV exposure, was significantly elevated (OR = 1.90, 95% CI: 1.07–3.39). These results, together with those of an earlier study, suggest that workers in heavy equipment and transport equipment operation may have increased risk of prostate cancer. Further investigation is warranted.

© The Author 2012. Published by Oxford University Press on behalf of the British Occupational Hygiene Society [2012]This ArticleAnn Occup Hyg (2012) 56 (8): 968-974. doi: 10.1093/annhyg/mes010 First published online: April 26, 2012 Current Issue

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Academy Instructor Benefits Cancer Victim

When David Sacks, a 42-year-old Philadelphia-based photographer was diagnosed last October with stage four cancer in his liver, lungs, bones and lymph nodes, a group of his friends decided to organize an art-themed fundraiser to help with medical costs and other needs for David, his wife Angie and their four children. That decision came to fruition over the weekend as about 500 people showed up for an art show to support David, including still-life artist and School of Fine Art instructor at Academy of Art University, Elana Hagler. The Academy instructor donated fifty percent of her proceeds to David’s cause. “It can be hard to go from a place of being self-sufficient to being dependent on other people, but they've made that transition really easy and wonderful, it's an incredible gift of their time and energy that they made this all happen." Sacks said. "Angie and I are very grateful."

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