Researchers identify the role of androgen in renal cell carcinoma

In patients with renal cell carcinoma (RCC), androgen signaling may control the movement of tumor cells and their invasion of different parts of the body, according to study results published in Nature Communications. This is the first study to outline the role of androgens in renal cancer, and may open the door to new treatment approaches that target the androgen receptor (AR), researchers predicted.

In addition, these researchers found that men were three times more likely to develop renal cancer compared to women, and if they did, were five times more likely to develop lung metastases. Their new conclusions about the role of androgen in this particular form of cancer may explain why.

“In kidney cancer, many studies have provided conflicting information,” said senior author Chawnshang Chang, PhD, the George Hoyt Whipple Distinguished Professor of Pathology, Urology, and Radiation Oncology, University of Rochester Medical Center, and Wilmot Cancer Institute, Rochester, NY.

“In some cases, AR expression has been associated with less malignancy,” he explained. “We were able to begin to sort out AR’s function in this one disease, showing that AR-positive kidney tumors are more likely to spread to the lungs and AR-negative tumors are more likely to spread to the lymph nodes.”

Over the past 10 years, Dr. Chang and his laboratory researchers have done extensive research on the link between cancer and the AR, which serves to bind male hormones, transcribe DNA, and plays a vital role in male sex characteristics. They have shown that AR plays a dual role in many different cancers, such as bladder cancer, in which AR can not only enhance bladder cancer cell invasion, but also suppress prostate cancer cell invasion.

For this recent study, they conducted an epidemiologic survey of almost 4,000 cases of kidney cancer in China, and found that men were almost three times more likely to develop renal cancer compared to women. In those in whom renal cancer spread to the lungs within 12 months, they found that the male-to-female ratio increased significantly, to nearly 5:1.

Gender differences were less significant, however, in patients whose cancer spread to the lymph nodes instead of the pulmonary system. This was presumably because the cancer cells contained fewer ARs.
In the next phase, Dr. Chang and colleagues will study human cells and tissue to understand how signaling between AR proteins works and interacts with other known cancer-associated genes to enhance or reduce metastasis.

Funding for this study was provided by the National Institutes of Health, the George H. Whipple Professorship Endowment, UR Department of Urology Research Fund, the Taiwan Ministry of Health and Welfare Clinical Trial and Research Center of Excellence, and the National High Technology Research and Development program of China.