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    Researchers Identify Gene That Can Play Key Role in Suppressing Growth of Melanoma Tumors

    Contact: Meg Walker, (415) 600-7674
    WalkerMX@sutterhealth.org

    Gene also may help determine risk of cancer spreading

    San Francisco, CA, January 30, 2013 – Researchers have identified a new role for a gene in the deadly skin cancer melanoma. Findings from the research article have been published in the Journal of the National Cancer Institute.

    It is the first time the function of the microRNA-18b gene (also referred to as miR-18b) has been described in controlling cancer cell growth, using melanoma as a model. The findings suggest that expressing the gene could be helpful in treating patients with melanoma and lead to developing new therapies for the disease. The study, “The Role of miR-18b in MDM2-p53 Pathway Signaling and Melanoma Progression” is scheduled to be online after 4 p.m. EST, Wednesday, Jan. 30, 2013, and in the March 20, 2013 print issue of the Journal of the National Cancer Institute.

    “We show that expressing miR-18b in melanoma cells has profound suppressive effects on tumor cell growth. We also show that measuring miR-18b levels may be useful to predict the risk of death due to the cancer,” said the corresponding author of the paper, Mohammed Kashani-Sabet, M.D., medical director for cancer programs at California Pacific Medical Center (CPMC), and medical director for the Center for Melanoma Research and Treatment at CPMC in San Francisco.

    The study was reported by Kashani-Sabet and colleagues from CPMC as well as researchers from the Department of Urology, Veterans Affairs Medical Center and University of California San Francisco.

    The researchers examined the role of the miR-18b gene in tissues from melanomas in humans and mice. They showed that the growth of melanoma cells in mice was dramatically slowed by overexpressing the miR-18b gene, suggesting it as a possible treatment approach. In addition, analysis of tissues from 140 human specimens indicated that the levels of miR-18b were significantly reduced in melanoma tissues when compared with benign moles. This suggests that miR-18b levels may be useful in helping to distinguish between benign moles and malignant melanomas. Finally, patients with melanomas expressing lower levels of miR-18b had significantly reduced survival when compared with those patients whose tumors expressed higher levels of the gene. This suggests that the levels of miR-18b can potentially be useful in helping to predict the prognosis of melanoma patients and to determine the risk of spread of their cancer.

    A key finding of the study was the identification of the way in which miR-18b exerts these effects on melanoma cells. The researchers showed that miR-18b directly targets and inactivates a gene called MDM2, which is important for cancer cell growth. Inactivation of MDM2 results in activation of the p53 gene, which regulates the cell cycle and has been widely studied for its role as a tumor suppressor that can control the growth of various cancers. Mutations in the p53 gene are commonly found in many cancers, and represent an important step in cancer development. However, melanoma is unique among human tumors in that p53 mutations are infrequently present. The loss of miR-18b in melanomas demonstrated in this study represents a novel mechanism responsible for loss of p53, helping to explain how the cancer can develop. Conversely, increasing levels of miR-18b in the melanoma tumor could result in shrinking the tumor because it re-activates the crucial p53 gene, the study concluded.

    “We learned that miR-18b, at increased levels, can suppress tumor growth due to its effect on these two other genes,’’ Kashani said.

    Next steps for this study include the analysis of levels of miR-18b in larger samples of benign moles and melanoma tumors.


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