Germline mutations identified in melanoma-prone kindreds can impair the function of the p14ARF tumour suppressor

在易患黑色素瘤的亲属中发现的种系突变可能会损害 p14ARF 肿瘤抑制因子的功能

• 批准号: nhmrc : 153887
• 负责人: Prof Helen Rizos
• 金额: $ 17.14万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2001
• 资助国家: 澳大利亚
• 起止时间: 2001-01-01 至 2003-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/germline-mutations-identified-tumour-suppressor/80755
• 关键词: Germline; mutations; identified; melanoma; prone

Approximately 10% of people in Australia are at high risk of developing melanoma because they carry a faulty gene. Many of these melanoma-prone individuals carry a single mutation that can disrupt two genes, p16INK4a and p14ARF. These genes are both involved in regulating the growth of cells via different pathways. The role of p16INK4a in cancer development is well established and the many functions of this gene are under intense investigation. In contrast, the role of p14ARF in melanoma progression has not been studied. We will be analysing in detail how faulty p14ARF promotes uncontrolled cell growth and cancer development. Our research, will dissect the functions of p14ARF and determine whether p14ARF and p16INK4a co-operate in maintaining normal cell growth. This work is essential to our understanding of melanoma development and will provide clinically useful information regarding the biology of human cancer.

在澳大利亚，大约10%的人患有黑色素瘤的风险很高，因为他们携带有缺陷的基因。这些容易患黑色素瘤的人中，许多人携带着一种单一的突变，这种突变可以破坏p16INK4a和p14ARF两个基因。这两个基因都通过不同的途径参与调节细胞的生长。P16INK4a在癌症发生发展中的作用已经确定，该基因的许多功能正在进行深入的研究。相比之下，p14ARF在黑色素瘤进展中的作用尚未被研究。我们将详细分析有缺陷的p14ARF如何促进不受控制的细胞生长和癌症发展。我们的研究将剖析p14ARF的功能，并确定p14ARF和p16INK4a是否在维持正常细胞生长方面协同作用。这项工作对我们理解黑色素瘤的发展是必不可少的，并将提供有关人类癌症生物学的临床有用信息。