Research reports from Genomics Research Center provide new insights into gene therapy
2007 NOV 19 -- Research findings, 'Human p16gamma, a novel transcriptional variant of p16(INK4A), coexpresses with p16(INK4A) in cancer cells and inhibits cell-cycle progression,' are discussed in a new report. According to a study from Taipei, Taiwan, "The INK4A locus encodes two tumor suppressor genes, p16(INK4A) and p14(ARF), transcribed using alternative exons 1alpha or 1beta spliced onto the same exons 2 and 3. Both p16(INK4A) and p14(ARF) are capable of inhibiting the cell-cycle progression, albeit in different manner; p16(INK4A) is phosphorylation of retinoblastoma (pRB) dependent while p14(ARF) is p53-dependent." "In this study, we report the discovery of a novel variant of p16(INK4A), termed p16gamma, in a primary T-cell acute lymphoblastic leukemia (T-ALL) patient sample and a neuroblastoma cell line, which was expressed at both the transcriptional and translational levels. Cloning and sequencing of the p16gamma cDNA revealed that p16gamma was identical to p16(INK4A), except that it contained an in-frame insertion of 197 bp between exons 2 and 3. p16gamma expression was detected in the majority of p16(INK4A)-expressing primary T-ALL and B-ALL patient samples and other p16(INK4A)-expressing tumor samples, but was only barely detectable in some normal mononuclear cells and other non-tumor samples. Structural analysis by nuclear magnetic resonance and circular dichroism confirmed that p16gamma, like p16(INK4A), is also an ankyrin-repeat protein. Functional analysis of p16gamma revealed that p16gamma protein interacted with cyclin D-dependent kinase4 and inhibited its kinase activity. Using a luciferase reporter assay, the transfection of p16gamma repressed the E2F response, the downstream target of pRB, with an efficacy equivalent to that of p16(INK4A)," wrote Y.C. Lin and colleagues, Genomics Research Center. The researchers concluded: "Moreover p16gamma, like p16(INK4A), induced cell-cycle arrest at G(0)/G(1), and inhibited cell growth in colony formation assay." Lin and colleagues published their study in Oncogene (Human p16gamma, a novel transcriptional variant of p16(INK4A), coexpresses with p16(INK4A) in cancer cells and inhibits cell-cycle progression. Oncogene, 2007;26(49):7017-27). For more information, contact Y.C. Lin, Genomics Research Center, Academia Sinica, Taipei, Taiwan. Publisher contact information for the journal Oncogene is: Nature Publishing Group, Macmillan Building, 4 Crinan St., London N1 9XW, England. Keywords: Taiwan, Taipei, Biotechnology, Cancer, Cloning, Gene Therapy, Genetics, Genomics, Oncology, Tumor Suppression. This article was prepared by Clinical Oncology Week editors from staff and other reports. Copyright 2007, Clinical Oncology Week via NewsRx.com.
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