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癌基因的myc家族及其在小细胞肺癌和其他肿瘤类型中的存在与重要性。

The myc family of oncogenes and their presence and importance in small-cell lung carcinoma and other tumour types.

作者信息

Prins J, De Vries E G, Mulder N H

机构信息

Department of Internal Medicine, University Hospital Groningen, The Netherlands.

出版信息

Anticancer Res. 1993 Sep-Oct;13(5A):1373-85.

PMID:8239508
Abstract

The myc family of cellular oncogenes, c-myc, N-myc, encodes three highly related, cell cycle specific, nuclear phospho-proteins. All are able to transform primary rat embryo fibroblasts when cotransfected with the c-ras oncogene. Myc family genes are differentially expressed with respect to tissue type and developmental stage and dramatic changes in their expression coincide with critical developmental transitions in many cell lineages. Their conservation as distinct genes over a large phylogenetic distance and their unique pattern of expression in developing embryos support the view that each member of the myc family may have an important and discrete biological activity. The nuclear localization and the presence of contiguous regions containing the basic region/helix-loop-helix/leucine zipper motifs suggest that myc-encoded proteins are involved in gene expression during growth and differentiation. The role of myc-oncogene amplification and/or overexpression in tumourigenesis is still not clear, but application of new biotechnological tools as transfection vectors and the antisense strategy may lead to a better understanding of the importance of the myc family of oncogenes. Transfection of cells with oncogenes in expression vectors conferring high levels of oncoprotein are used to analyze the influence of overexpression of the oncogene, while incubation with an appropriate antisense oligonucleotide leading to an inhibition of oncogene expression may give some clues to the necessity, function and importance of the oncogene. These two techniques have proven to be useful tools in the illumination of the function of these ubiquitous (proto-) oncogenes and probably will help to clarify at least a part of their role in, for instance, apoptosis, tumourigenesis and the development of resistance to antitumour drugs.

摘要

细胞癌基因的myc家族,包括c-myc、N-myc,编码三种高度相关、细胞周期特异性的核磷蛋白。当与c-ras癌基因共转染时,它们都能够转化原代大鼠胚胎成纤维细胞。Myc家族基因在组织类型和发育阶段方面存在差异表达,其表达的显著变化与许多细胞谱系中的关键发育转变相一致。它们在很大的系统发育距离上作为不同基因得以保守,以及在发育胚胎中独特的表达模式支持了这样一种观点,即myc家族的每个成员可能都具有重要且独特的生物学活性。核定位以及包含碱性区域/螺旋-环-螺旋/亮氨酸拉链基序的连续区域的存在表明,myc编码的蛋白质参与生长和分化过程中的基因表达。myc癌基因扩增和/或过表达在肿瘤发生中的作用仍不清楚,但应用诸如转染载体和反义策略等新的生物技术工具可能会有助于更好地理解myc癌基因家族的重要性。用赋予高水平癌蛋白的表达载体中的癌基因转染细胞,用于分析癌基因过表达的影响,而用适当的反义寡核苷酸孵育导致癌基因表达受到抑制,可能会为癌基因的必要性、功能和重要性提供一些线索。这两种技术已被证明是阐明这些普遍存在的(原)癌基因功能的有用工具,并且可能至少有助于澄清它们在例如细胞凋亡、肿瘤发生和抗肿瘤药物耐药性发展中的部分作用。

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