Gene expression changes induced upon Beta3 integrin expression in human melanoma metastasis

人黑色素瘤转移中 Beta3 整合素表达诱导的基因表达变化

• 批准号: nhmrc : 102565
• 负责人: A/Pr Richard Sturm
• 金额: $ 13.3万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2000
• 资助国家: 澳大利亚
• 起止时间: 2000-01-01 至 2002-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/gene-expression-changes-melanoma-metastasis/77646
• 关键词: Gene; expression; changes; induced; upon

Diagnostic and prognostic markers for metastatic melanoma are essential to better understand the development of this cancer. One of the most effective markers so far found to correlate with invasiveness of tumour cells, and hence lethality of melanoma, is the Beta3 integrin molecule. When this protein is expressed on the surface of early stage melanoma cells, that in themselves are not able to form metastatic tumours, they convey upon the cells the ability to proceed from growing on the surface of the skin (radial growth phase) to allowing them to invade the skin (vertical growth phase). It is not clear how expression of Beta 3 allows this change in growth state to occur and this research program is designed to test if Beta 3 is the direct cause of gene expression changes mediating the metastatic transformation. To provide insight into the genetic changes induced in melanoma cells expressing the Beta3 protein a screen for genes that are either activated or repressed in the presence of Beta3 will be performed. Non-metastatic melanoma cells will be transduced with the Beta 3 gene and a molecular technique applied to these cells that can identify genetic differences which will allow the cloning of differentially expressed genes. The gene fragments that are identified will first provide clues as to what the genes are that maybe switched on or off to allow the tumour to grow beneath the skin. They will also form the basis of a Ometastatic melanoma gene panelO that can be tested for its diagnostic value of tumours. The utility and reproducibility of the gene panel will be confirmed by testing melanoma cell lines and tumour tissue. These experiments should lead to better diagnosis of metastatic melanoma and also possible new avenues to develop therapies for the disease.

转移性黑色素瘤的诊断和预后标志物对于更好地了解这种癌症的发展至关重要。迄今为止发现的与肿瘤细胞的侵袭性相关的最有效的标志物之一，因此黑色素瘤的致死性，是β 3整联蛋白分子。当这种蛋白质在本身不能形成转移性肿瘤的早期黑素瘤细胞的表面上表达时，它们向细胞传递从在皮肤表面上生长（径向生长期）到允许它们侵入皮肤（垂直生长期）的能力。目前尚不清楚β 3的表达如何允许生长状态发生这种变化，本研究计划旨在测试β 3是否是介导转移性转化的基因表达变化的直接原因。为了深入了解表达β 3蛋白的黑素瘤细胞中诱导的遗传变化，将筛选在β 3存在下被激活或抑制的基因。非转移性黑色素瘤细胞将用β 3基因转导，并将分子技术应用于这些细胞，该技术可以鉴定遗传差异，这将允许克隆差异表达的基因。被识别的基因片段将首先提供线索，说明哪些基因可能被打开或关闭，以允许肿瘤在皮肤下生长。它们也将形成转移性黑色素瘤基因组的基础，该基因组可被测试其肿瘤诊断价值。将通过检测黑色素瘤细胞系和肿瘤组织来确认基因组的实用性和再现性。这些实验将有助于更好地诊断转移性黑色素瘤，并可能为该疾病的治疗开辟新的途径。