Novel molecular processes controlling key genes in prostate cancer uncovered

March 7, 2016, Karolinska Institutet
Micrograph showing prostatic acinar adenocarcinoma (the most common form of prostate cancer) Credit: Wikipedia

Researchers at Sweden's Karolinska Institutet and the University of Oulu in Finland have elucidated gene regulatory mechanisms that can explain how known genetic variants influence prostate cancer risk. The findings, published in the journal Nature Genetics, reveal widespread deregulation of androgen receptor function, a key player in prostate cancer.

The vast majority of the three billion base-pairs in the human genome are identical across individuals. Nevertheless, genome sequence variation that does occur in the population has a profound effect on an individual's predisposition for developing various diseases. In the case of , 100 regions of have been identified through comparative genetic studies. Each have a small but significant influence on . Previous studies have demonstrated an association of these genomic regions with disease, but the molecular processes accounting for the disease association have not yet been uncovered for most of these 100 regions.

Using computational and statistical analysis, Thomas Whitington and colleagues at Karolinska Institutet devised a method for analysing the molecular processes at these . The researchers identified mechanisms that can explain many of the known associations between genetic variation and prostate cancer risk. These discoveries were validated using molecular techniques by a research team led by Gong-Hong Wei at University of Oulu.

"In particular, we discovered that binding of physical complexes involving the androgen receptor, a key transcription factor in prostate cancer, is often disrupted by DNA sequence variation associated with the disease", says Thomas Whitington at the Department of Medical Epidemiology and Biostatistics at Karolinska Institutet, one of the researchers behind the study.

Transcription factors are key molecular components of the cell that bind to DNA and affect the activity of nearby genes. The androgen receptor is a transcription factor that promotes proliferation and survival of . In the current study, the investigators found that binding of androgen receptor at these locations of genetic variation was frequently tumor-specific, and not present in normal prostate tissue.

"This work refines our understanding of how this molecular machinery is involved in disease processes", says Thomas Whitington. "An improved understanding of binding may in particular prove useful, as it's activity becomes pivotal during the treatment of late stage aggressive prostate cancer."

Explore further: Prostate cells undergo 'reprogramming' to form tumors, study finds

More information: 'Gene regulatory mechanisms underpinning prostate cancer susceptibility', Thomas Whitington, Ping Gao, Wei Song, Helen Ross-Adams, Alastair Lamb, Yuehong Yang, Ilaria Svezia, Daniel Klevebring, Ian Mills, Robert Karlsson, Silvia Halim, Mark Dunning, Lars Egevad, Anne Warren, David Neal, Henrik Grönberg, Johan Lindberg, Gong-Hong Wei, Fredrik Wiklund, Nature Genetics, online 7 March 2016, DOI: 10.1038/ng.3523

Related Stories

Prostate cells undergo 'reprogramming' to form tumors, study finds

October 12, 2015
Scientists have gained a key insight into how prostate tumors get their start - not by rewriting the normal DNA code, but by reprogramming the master regulator of genes in prostate cells to drive malignant growth.

Prostate cancer discovery may make it easier to kill cancer cells

December 18, 2015
A newly discovered connection between two common prostate cancer treatments may soon make prostate cancer cells easier to destroy. Drugs that could capitalize on the discovery are already in the pipeline, and a clinical trial ...

New genetic discovery advances understanding of prostate cancer

October 26, 2015
A new and important genetic discovery, which sheds light on how prostate cancers develop and spread, has been made by an international research team led by scientists at The University of Nottingham.

Mechanism affecting risk of prostate cancer is found

January 10, 2014
A research group at Biocenter Oulu in Finland has identified a mechanism related to a transcription factor that binds much more strongly onto a particular SNP variant, thereby initiating a genetic programme which enhances ...

Why combined therapies increase survival in prostate cancer

November 6, 2015
Researchers at Karolinska Institutet, SciLifeLab and Centre for Clinical Research, Västerås have been able to explain why a combination of castration therapy and radiation therapy increases survival rates for patients with ...

Prostate cancer: Androgen receptor activates different genes when bound to antiandrogens

January 27, 2015
The androgen receptor in prostate cancer cells can activate different sets of genes depending on whether it binds with an androgen hormone or an antiandrogen drug, according to a new study led by researchers at The Ohio State ...

Recommended for you

Breast cancer researcher warns against online genetic tests

June 18, 2018
We have never been so fascinated by the secrets inside our cells.

Genomics offers new treatment options for infants with range of soft tissue tumors

June 18, 2018
The genetic causes of a group of related infant cancers have been discovered by scientists at the Wellcome Sanger Institute, the University of Wuerzburg and their collaborators. Whole genome sequencing of tumours revealed ...

Non-coding DNA reveals a route by which advanced prostate cancer resists treatment

June 15, 2018
Two research teams converge on epigenetic switches that feed treatment-resistant metastatic prostate tumors. This research highlights the value of exploring gene regulation and large-scale structural changes in the cancer ...

Researchers peer inside cells to spy on cancer's on-off switch

June 15, 2018
Forty years after researchers first discovered it in fruit flies, a once-obscure cluster of proteins called PRC2 has become a key target for new cancer-fighting drugs, due to its tendency—when mutated—to bind to and silence ...

PIM-2 protein kinase regulates T-cell activity differently than PIM-1 or PIM-3 isoform

June 15, 2018
The PIM-2 protein kinase negatively regulates T cell responses in transplantation and tumor immunity, while PIM-1 and PIM-3 are positive regulators, report Medical University of South Carolina (MUSC) investigators in an article ...

Gene testing could identify men with prostate cancer who may benefit from immunotherapy

June 14, 2018
Scientists have identified a pattern of genetic changes that could pick out men with advanced prostate cancer who are likely to benefit from immunotherapy.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.