Osteogenic Biomarker Abnormally Expressed in Aggressive Prostate Cancer

April 22, 2015

The osteogenic protein known as runt-related transcription factor 2 (RUNX2), appears to be abnormally expressed in prostate cancer and may be associated with metastatic disease, according to researchers at the University of Michigan.

The osteogenic protein known as runt-related transcription factor 2 (RUNX2), appears to be abnormally expressed in prostate cancer and may be associated with metastatic disease, according to researchers at the University of Michigan. They published  a study in the April 13, 2015 issue of Oncogene, suggesting that this biomarker may be a potentially important advance in diagnosing and treating prostate cancer.

Study investigator Renny Franceschi, PhD, who is a professor of dentistry, biological chemistry, and biomedical engineering at the University of Michigan, Ann Arbor, Mich., said there is great deal of interest in trying to identify biomarkers that can discriminate between aggressive and nonaggressive disease. He said if this biomarker controls the growth of prostate cells, it would be a new signal that's not been seen before, and could provide a potential new drug target for prostate cancer.

Adding a phosphate group--which is known as phosphorylation--to the protein RUNX2, changes its structure to activate specific genes in both bone and prostate cancer cells, but with vastly different results. Bone cells need RUNX2 and the newly roused genes to make healthy bone. However, RUNX2 appear to trigger genes that fuel tumor growth and metastasis in prostate cancer cells, according to the researchers.

Dr. Franceschi and colleagues discovered this regulatory mechanism in bone cells. In cancer cells, they inhibited the ability of RUNX2 to be phosphorylated and they found that tumor growth was reduced. Franceschi's lab also collaborated with researchers in Italy to analyze tissue samples from 129 patients with prostate cancer. The researchers found little or no RUNX2 phosphorylation in normal prostate samples, suggesting that RUNX2 phosphorylation is closely associated with the more aggressive forms of prostate cancer. 

The tissue microarrays from 129 patients revealed strong nuclear staining with the RUNX2 antibody in primary prostate cancer and metastases. The researchers found that RUNX2 staining was positively correlated with Gleason score and occurrence of lymph node metastases. The group found that little or no RUNX2 phosphorylation was seen in normal prostate, benign prostate hyperplasia (BPH), or prostatitis.

The investigators concluded that these studies establish "the importance of RUNX2 phosphorylation in prostate tumor growth and highlight its value as a potential diagnostic marker and therapeutic target." They say the next step is to establish an actual cause-and-effect relationship between RUNX2 phosphorylation and prostate cancer. During their next round of testing, they hope to compare prostate cancer formation in animal models lacking RUNX2 in their prostates.

Prostate cancer is the second most common cancer in men worldwide, according to the American Cancer Society. It is estimated that in the US, approximately 221,000 new cases of prostate cancer will be diagnosed in 2015, resulting in roughly 27,500 deaths.

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