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Aug 12, 2009

Researchers Implicate RAMP as Oncogene in Gastric Cancer

  • A protein known as RAMP (retinoic acid-regulated nuclear matrix-associated protein) plays an oncogenic role in stomach cancer, according to scientists at the Chinese University of Hong Kong. They found the protein promoted cancer cell growth, and increased levels of RAMP were evident in stomach cancer even during very early stages of the disease.

    Conversely, when RAMP was knocked out of human gastric cancer cell lines, cancer growth was inhibited and cancer cell death occurred. The findings are published in the August issue of the British Journal of Cancer in a paper titled “Identificaiton of retinoic acid-regulated nuclear matrix-associated protein as a novel regulatory of gastric acid.”

    RAMP expression was evaluated with real-time quantitative RT-PCR, immunohistochemistry, and western blotting. Inhibition of RAMP was performed by siRNA-mediated knockdown. The functional effects of RAMP on cell kinetics were measured by cell viability assay, colony formation assay, and flow cytometry. Cell lines stably expressing RAMP were established to investigate the oncogenic effects of RAMP in vitro.

    RAMP was expressed in all seven gastric cancer cell lines and was significantly increased in human gastric cancer tissues when compared with their adjacent noncancerous tissues, the investigators report.

    Additionally, knockdown of RAMP in gastric cancer cells significantly reduced cell proliferation and soft agar colony formation but induced apoptosis. This induced cell apoptosis was dependent on functional accumulation of p53 and p21 and induction of cleaved caspases-9, caspases-3, and PARP. Also, overexpression of RAMP promoted anchorage-independent cell growth in soft agar.

     “The next stage of our research will aim to discover more about RAMPs specific role in stomach cancer and begin exploring the possibility of developing new drugs that can stop RAMP in its tracks,” comments study author, Dr. WK Leung.

     



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