Discovery of a new cancer gene, which, when damaged, may promote prostate cancer

Nov 24 2004

Together with an international research team, researchers from VTT Technical Research Centre of Finland have developed an effective method for the screening and identification of genes that under normal conditions suppress cancer growth.

The method enabled the discovery of a new cancer gene, which, when damaged, may promote prostate cancer. Prostate cancer is the most diagnosed form of cancer in men; it is also becoming increasingly common. Thus, this finding may have great significance for the development of new forms of therapy.

The researchers developed a method for the effective screening and identification of tumor growth-suppressing genes and their mutations. With the new technique, it is possible to identify potential tumor-suppressor genes from among the approximately 25,000 human genes and accelerate research significantly. The new microarray-based method allows the efficient screening of thousands of genes in a single laboratory experiment.

The effectiveness of the method is due to the combination of two screening methods: the NMD (nonsense-mediated mRNA decay) microarray technique is used to screen for mutated genes, while the CGH (comparative genomic hybridization) microarray technique is used to screen for DNA copy number losses from the same sample. By combining these findings researchers can efficiently pinpoint those genes whose function has failed in cancer cells

Using this novel approach the researchers were able to find errors in the EPHB2 gene. The gene encodes a cell membrane receptor, which has a role in the intracellular communication, and is required for cell differentiation, cell mobility and maintenance of correct tissue structure. A defect in the EPHB2 gene function may thus cause tissue dysorganization and promote the proliferation and metastatis of cancer cells. This finding helps to provide a better understanding of the molecular mechanisms involved in the development and progression of cancer, which is an essential step in the development of novel anti-cancer therapies.

Researchers found mutations in EPHB2 gene in 8% of prostate cancer patients, particularly in the metastatic tumors. The discovery is hoped to facilitate the development of novel therapeutics for prostate cancer. The researches aim to develop the novel NMD-CGH microarray method further and apply it for new tumor-suppressor gene discovery approaches in prostate cancer and other cancer types.

Launched three years ago at the National Institutes of Health (NIH) in the United States, the research was continued in Finland at VTT in the Medical Biotechnology Department, in collaboration with a research team at the Translational Genomics Research institute in the US.

Prostate cancer is the most common cancer in men, the incidence of which has shown an increasing trend over the past few years. The origins of prostate cancer remain largely unknown, however, researchers believe that genetic errors occurring in prostate cells during the aging process have a significant impact. The loss of function of the tumor-suppressor genes plays a major role in the development of cancer. So far approximately twenty such genes have been identified in the human genome. Their normal function ensures the correct growth of cells and prevents the proliferation of cancer cells in the body.