Scientists pinpoint estrogen as key player in half of all prostate cancers

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Washington, May 28 : Estrogen, known as a 'female hormone', plays a crucial role in the development of almost half of all prostate cancers, a new study has revealed.

The researchers, led by Dr. Mark A. Rubin, professor of pathology and laboratory medicine, and vice chair for experimental pathology at Weill Cornell Medical College, also said that estrogen-linked signalling helps initiate a discrete and aggressive form of the disease caused by a chromosomal translocation, which in turn results in the fusion of two genes.

"Fifty percent of prostate cancers harbour a common recurrent gene fusion, and we believe that this confers a more aggressive nature to these tumours. Interfering with this gene fusion - or its downstream molecular pathways - will be crucial in the search for drugs that fight the disease. Based on our new data, we now believe that inhibiting estrogen may be one way of doing so," said Rubin.

Earlier, Rubin, along with researchers at the University of Michigan, discovered and described the common fusions between the TMPRSS2 and ETS family member genes subset of prostate cancer.

"The discovery showed that these malignancies occur after an androgen (male hormone)-dependent gene fuses with an oncogene - a type of gene that causes cancer," he explained.

While it has long been known that male hormones help spur prostate cancer and thus androgen-deprivation therapy is suggested as the first-line treatment against the disease. But still, the disease can progress despite androgen reduction, suggesting that other pathways might be at work.

"So, we wanted to learn more - what is the genetic and molecular 'fingerprint' of this aggressive subset of prostate tumor?" said Rubin.

For this, the researchers analysed 455 prostate cancer samples from trials in Sweden and the United States that were conducted in mid-1970s.

"These samples were placed in fixative and not frozen, so we needed new methods of retrieving the genetic information," said Rubin.

Thus, they developed an innovative technology for effectively "reading" the gene transcription profiles hidden in the samples.

"That led us to perform the largest gene-expression microarray analysis yet conducted in prostate cancer research, amassing information on more than 6,000 genes. This allowed us to obtain a robust, 87-gene expression 'signature' that distinguishes fusion-positive TMPRSS2-ERG cancers from other prostate malignancies," said Rubin.

After a close analysis of the signature, it was surprisingly found that estrogen-dependent molecular pathways play a crucial role in regulating (and encouraging) this aggressive subset of prostate cancer. Although estrogen is typically thought of as a "female" hormone, it sis aloso produced by men.

"Now, we show for the first time that this natural estrogen can stimulate the production of the cancer-linked TMPRSS2-ERG transcript, via the estrogen receptor (ER)-alpha and ER-beta. These receptors are found on the surface of some prostate cancer cells," explained Rubin.

This unique finding could have implications for prostate cancer research, including drug development.

The study is published in the latest online edition of the Journal of the National Cancer Institute.

ANI

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