耶鲁大学发现一种调节基因是黑色素瘤的靶标

 
癌症研究人员发现：MITF（小眼畸形相关转录因子）主要调节基因在恶性黑色素瘤中高度增强，可能是化疗的一个靶标。

耶鲁大学的研究人员使用HistoRx整合AQUA（自动定量分析）系统分析了在NCI160黑色素瘤细胞培养中的基因数量。AQUA是一种联合了荧光影像、自动显微镜和高通量组织微阵列技术的系统。

研究人员在2005年7月7日《自然》杂志上报道说，黑色素瘤主要调节子MITF是新的黑色素瘤扩大的靶标。MITF扩大在转移性疾病十分普遍，与患者总生存率下降有关。MITF基因多拷贝表达，增加了黑色素瘤细胞对化疗药物的抵抗性。因此，设计能够抑制该基因扩增的药物，能够提高抗癌药物的敏感性。

耶鲁医学院病理学副教授David Rimm博士说：“根据这项研究，这些资料提示MITF代表了一类“世系生存”或者“世系增加”肿瘤基因，这种基因在组织特异性发育和肿瘤进展中是必须的。

Regulator Gene a Melanoma Target
 
Cancer researchers have found that the MITF (microphthalmia-associated transcription factor) master regulator gene is highly amplified in malignant melanoma and presents an attractive target for chemotherapy.

Investigators at Yale University (New Haven, CT, USA) used the new HistoRx Incorporated (New Haven, CT, USA) AQUA (Automated Quantitative Analysis) System to analyze gene numbers in cultures of NCI160 melanoma cells. AQUA is a system that combines fluorescence-based imaging with automated microscopy and high-throughput tissue microarray technologies.

The researchers reported in the July 7, 2005, issue of Nature that the melanocyte master regulator MITF was the target of novel melanoma amplification. MITF amplification was more prevalent in metastatic disease and correlated with decreased overall patient survival. Expression of multiple copies of the MITF gene enhanced the ability of the melanoma cells to develop resistance to chemotherapy. Therefore, drugs designed to prevent amplification of the gene would increase sensitivity to anti-cancer drugs.

“According to the study, these data suggest that MITF represents a distinct class of ‘lineage survival’ or ‘lineage addiction’ oncogenes required for both tissue-specific development and tumor progression,” said contributing author Dr. David Rimm, associate professor of pathology at the Yale School of Medicine.