Isolation of a rearranged human transforming gene following transfection of Kaposi sarcoma DNA.

Isolation of a rearranged human transforming gene following transfection of Kaposi sarcoma DNA.
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转染卡波西肉瘤 DNA 后重排的人类转化基因的分离。

DOI:
10.1073/pnas.84.16.5660
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发表时间:
1987
影响因子:
11.1
通讯作者:
Basilico,C
Basilico,C
中科院分区:
综合性期刊1区
文献类型:
--
作者:
DelliBovi,P;Basilico,C

文献摘要

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通过将来自卡波西肉瘤病变的高分子量DNA转染到小鼠NIH 3T3细胞中,我们已经鉴定并分子克隆了一组能够在这些细胞中诱导病灶形成、琼脂生长和致瘤性的人类DNA序列。在一、二、三级NIH 3T3转化体中存在的人类DNA序列包含约32千碱基(kb),并且包含与正常人类DNA和一部分c-fms原癌基因(人类基因命名法中的FMS)相关的四个重排。然而,在我们克隆的DNA中发现的最小转化区(6.6 kb)与c-fms DNA区域相邻,但不包含c-fms编码序列。在NIH 3T3转化子中检测到的两个转录本(大约等于1.2和3.5 kb)中也没有fms序列;然而,它们可能提供调节表达的元素。对几个已知的癌基因探针的杂交和初步测序数据表明,我们已经确定了一个以前未被识别的“激活”癌基因。由于我们克隆的DNA序列中的重排在用于转染的原始卡波西肿瘤DNA中未检测到,因此该致癌基因可能是在基因转移过程中产生的。
By transfecting high molecular weight DNA from a Kaposi sarcoma lesion into murine NIH 3T3 cells, we have identified and molecularly cloned a set of human DNA sequences capable of inducing focus formation, growth in agar, and tumorigenicity in these cells. The human DNA sequences present in primary, secondary, and tertiary NIH 3T3 transformants encompass about 32 kilobases (kb) and contain four rearrangements with respect to normal human DNA and a portion of the c-fms protooncogene (FMS in human gene nomenclature). However, the minimal transforming region (6.6 kb) identified in our cloned DNA borders on the c-fms DNA region but does not contain c-fms coding sequences. The fms sequences are also not represented in the two transcripts (approximately equal to 1.2 and 3.5 kb) detected in NIH 3T3 transformants; however, they might provide elements regulating expression. Hybridization to several known oncogene probes and preliminary sequencing data indicate that we have identified a previously unrecognized "activated" oncogene. Since the rearrangements present in our cloned DNA sequences are not detectable in the original Kaposi tumor DNA used for transfection, it is possible that this oncogene was generated during gene transfer.