New oncogene linked to prostate cancer in African Americans may lead to better diagnostic tools

October 21, 2016, Baylor College of Medicine
Increased lipogenesis (formation of fatty acids, in red) in prostate cancer cells. Lipids act as important energy storage during the spread of cancer. Therapies that disrupt lipogenesis or inhibit oncoproteins that enhance fatty acid biosynthesis could potentially block tumor metastasis. Nucleus of the cell is stained blue. Credit: National Cancer Institute / Duncan Comprehensive Cancer Center at Baylor College of Medicine / Subhamoy Dasgupta.

A team of scientists has identified MNX1 as a new oncogene - a gene than can cause cancer - that is more active in African American prostate cancer than in European American prostate cancer. The finding suggests that genetic factors can contribute, at last in part, to the higher incidence of prostate cancer among African American men compared with men of other ethnic groups. The team includes scientists at Baylor College of Medicine, Third Military Medical University in China, the Michael E. DeBakey VA Medical Center, and Agilent Technologies India Pvt. Ltd. The study appeared Aug. 31 in Cancer Research.

"African Americans have about one-and-a-half times the incidence and twice the mortality associated with prostate cancer of European Americans, and the reasons for this are not clear," said senior author Dr. Michael Ittmann, professor of pathology & immunology at Baylor and the Michael E. DeBakey Department of VA Medical Center.

Most scientists think that some of the health disparities among can be explained by differences in biology. Socio-economic factors, such as unequal access to healthcare services that make African American men less likely to receive regular physical examinations and screening for prostate cancer, may also be involved.

To study the genetic differences between African American prostate cancer and European American prostate cancer, the scientists took advantage of the tremendously diverse resources available at the Dan L Duncan Comprehensive Cancer Center at Baylor, which include one of the most extensive African American prostate tissue banks.

"We determined the gene expression profiling of African American prostate cancers," said Ittmann, "and compared it with that of normal prostate tissue. Then, in collaboration with Dr. Chad Creighton, associate professor of medicine at Baylor and member of the Dan L Duncan Comprehensive Cancer Center Division of Biostatistics, we compared the gene expression profiling of African American prostate cancers with that of European American prostate cancers, which is available in published datasets."

"We found 24 genes that were different between the African American and the European American prostate cancer datasets," said Ittmann. "Some of the genes were less active in African American prostate cancer, but we concentrated on those that were more active as they could potentially be oncogenes. MNX1 was at the top of the list."

MNX1 had been previously described as an oncogene linked to infantile acute myeloid leukemia, a rare cancer of the bone marrow and lymph nodes.

"Our study so far suggested that MNX1 was likely an oncogene in prostate cancer. The protein the MNX1 gene produces is a transcription factor; it can turn on gene transcription in other genes, which results in those genes producing more of their proteins. So we went on and studied MNX1 more extensively," said Ittmann.

The scientists discovered that, compared with normal prostate tissues, both African American and European American prostate cancer have MNX1 genes that are more active and produce more of the MNX1 protein. However, MNX1 is significantly more active in African American prostate cancer than in European American prostate cancer.

Further research shed light on what can increase MNX1 activity in prostate cancer and strengthened MNX1's ties to the disease.

"Interestingly, we found that both androgens, such as testosterone, and AKT, a signaling pathway, increase MNX1 activity. It's been known for quite some time that androgens and the AKT pathway play a central role in prostate cancer," said Ittmann.

The scientists then determined whether increased MNX1 activity affected a metabolic pathway prostate cancer uses to grow. Dr. Arun Sreekumar, professor of molecular and cellular biology, who also is with the Alkek Center for Molecular Discovery and the Verna and Marrs McLean department of biochemistry and molecular biology at Baylor, performed lipid analysis in African American prostate cancer tissues and showed that products of lipid metabolism increased when compared with those of normal prostate tissues.

"I am excited that these data highlight the existence of a biological basis in health disparity in prostate cancer," said Sreekumar.

In summary, in African American prostate cancer androgen and the AKT signaling pathway can increase the activity of MNX1, which in turn increases lipid metabolism. Increased lipid metabolism is a hallmark of aggressive prostate cancer, which is more common on African American men.

These results can potentially lead to new approaches to treat and diagnose prostate cancer. For instance, currently, there are medications available to control lipid synthesis, which allows for exploring the effect of targeting lipid synthesis on prostate cancer growth. The scientists will also explore whether MNX1 can help predict cases of aggressive prostate cancer in the clinic.

"The better we can understand different subsets of prostate cancer, for instance, from African American men, the better we can treat them. A "one-size-fits-all" approach to treatment may not work for all patients," said Creighton.

Explore further: African-American men negatively impacted by hormone therapy for treatment of prostate cancer

More information: L. Zhang et al, MNX1 Is Oncogenically Upregulated in African-American Prostate Cancer, Cancer Research (2016). DOI: 10.1158/0008-5472.CAN-16-0087

Related Stories

African-American men negatively impacted by hormone therapy for treatment of prostate cancer

August 4, 2016
In a retrospective study analyzing patients' medical records, researchers at Brigham and Women's Hospital found that patients' race significantly affected their longevity by increasing the likelihood of death after receiving ...

MRI feasible for predicting prostate CA in unselected sample

July 18, 2016
(HealthDay)—Prostate multiparametric magnetic resonance imaging (MRI) is feasible for predicting prostate cancer in an unselected sample of the general population, according to a study published in the August issue of The ...

New findings concerning hereditary prostate cancer

July 11, 2016
It is a well-known fact that men with a family history of prostate cancer run an increased risk of developing the disease. The risk for brothers of men with prostate cancer is doubled. But a doubled risk of what, exactly? ...

Prostate cancer tied to higher colorectal cancer risk

March 1, 2016
(HealthDay)—The risk of colorectal cancer is increased after a diagnosis of prostate cancer, according to a study published online Feb. 25 in Cancer.

Genomic fingerprint may predict aggressive prostate cancer in African-Americans

July 20, 2015
African American men are more likely to develop prostate cancer than European American men, and are also more than twice as likely to die from it. Although there are many reasons that contribute to this health disparity, ...

Early-onset baldness in African-American men may be linked to prostate cancer

March 26, 2013
Baldness was associated with an increased risk of prostate cancer among African-American men, and risk for advanced prostate cancer increased with younger age and type of baldness, according to data published in Cancer Epidemiology, ...

Recommended for you

Study tracks evolutionary transition to destructive cancer

February 23, 2018
Evolution describes how all living forms cope with challenges in their environment, as they struggle to persevere against formidable odds. Mutation and selective pressure—cornerstones of Darwin's theory—are the means ...

Researchers use a molecular Trojan horse to deliver chemotherapeutic drug to cancer cells

February 23, 2018
A research team at the University of California, Riverside has discovered a way for chemotherapy drug paclitaxel to target migrating, or circulating, cancer cells, which are responsible for the development of tumor metastases.

Lab-grown 'mini tumours' could personalise cancer treatment

February 23, 2018
Testing cancer drugs on miniature replicas of a patient's tumour could help doctors tailor treatment, according to new research.

An under-the-radar immune cell shows potential in fight against cancer

February 23, 2018
One of the rarest of immune cells, unknown to scientists a decade ago, might prove to be a potent weapon in stopping cancer from spreading in the body, according to new research from the University of British Columbia.

Putting black skin cancer to sleep—for good

February 22, 2018
An international research team has succeeded in stopping the growth of malignant melanoma by reactivating a protective mechanism that prevents tumor cells from dividing. The team used chemical agents to block the enzymes ...

Cancer risk associated with key epigenetic changes occurring through normal aging process

February 22, 2018
Some scientists have hypothesized that tumor-promoting changes in cells during cancer development—particularly an epigenetic change involving DNA methylation—arise from rogue cells escaping a natural cell deterioration ...

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.