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

The myc family of oncogenes and their presence and importance in small-cell lung carcinoma and other tumour types.
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发表时间:
1993-09
影响因子:
2
通讯作者:
J. Prins;E. de Vries;N. Mulder
J. Prins;E. de Vries;N. Mulder
中科院分区:
医学4区
文献类型:
--
作者:
J. Prins;E. de Vries;N. Mulder

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细胞癌基因的myc家族,c-myc, N-myc,编码三种高度相关的,细胞周期特异性的核磷酸化蛋白。当c-ras癌基因共转染时,它们都能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,其表达的巨大变化与许多细胞系的关键发育转变一致。它们作为不同基因在大的系统发育距离上的保存以及它们在发育胚胎中的独特表达模式支持了myc家族的每个成员可能具有重要而离散的生物活性的观点。细胞核定位和包含基本区/螺旋-环-螺旋/亮氨酸拉链基序的连续区域的存在表明myc编码蛋白参与了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尚不清楚,但应用新的生物技术工具作为转染载体和反义策略可能会更好地理解myc癌基因家族的重要性。将癌基因转染到高水平癌蛋白表达载体中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的抑制,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,并且可能有助于阐明它们在细胞凋亡、肿瘤发生和抗肿瘤药物耐药性发展中至少部分的作用。
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.