ras gene mutations in human prostate cancer.
ras gene mutations in human prostate cancer.
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DOI：
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发表时间：
1990-11
期刊：
影响因子：
11.2
通讯作者：
B. Carter;J. I. Epstein;W. Isaacs
中科院分区：
文献类型：
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作者：
B. Carter;J. I. Epstein;W. Isaacs
Ha-、Ki-和N-ras基因第12、13或61密码子的点突变能够将这些正常细胞基因转化为激活的癌基因。以往的研究表明，ras基因突变存在于多种人类实体肿瘤中，并可能在其中一些肿瘤的发病机制中起重要作用。为了验证ras基因突变可能与前列腺癌相关的假说，我们使用寡核苷酸杂交法检测了前列腺癌和前列腺癌细胞系基因组DNA中的野生型和突变型等位基因。对24例原发性前列腺肿瘤(23例腺泡肿瘤和1例导管肿瘤)和5株前列腺肿瘤细胞系进行了Ki-ras、Ha-ras和N-ras基因第12、13和61密码子的突变检测。在前列腺癌中检测到两个突变：A-G突变导致Ha-ras基因第61位密码子的谷氨酰胺到精氨酸氨基酸替换；G-T颠换导致Ha-ras基因第12位密码子的甘氨酸到Valine氨基酸替换。虽然ras基因突变在前列腺癌中的总体频率很低，但当这些突变确实发生时，它们可能在疾病的进展或前列腺癌的罕见导管变种的发展中发挥作用。
Point mutations at codons 12, 13, or 61 of the Ha-, Ki-, and N-ras genes are able to convert these normal cellular genes into activated oncogenes. Previous studies have shown that ras gene mutations occur in a variety of human solid tumors and may be important in the pathogenesis of some of these tumors. In order to test the hypothesis that ras gene mutations may be associated with prostate cancer, we have used an oligodeoxynucleotide hybridization assay to detect wild-type and mutant alleles in genomic DNA from prostate tumors and prostate tumor cell lines amplified using the polymerase chain reaction. Twenty-four primary prostate tumors (23 acinar tumors and one ductal tumor) and five prostate tumor cell lines were examined for mutations at codons 12, 13, and 61 of the Ki-ras, Ha-ras, and N-ras genes. Two mutations were detected: an A----G transition causing a glutamine to arginine amino acid substitution at codon 61 of the Ha-ras gene in a primary prostatic duct adenocarcinoma and a G----T transversion causing a glycine to valine amino acid substitution at codon 12 of the Ha-ras gene in a prostate tumor cell line (TSU-PR1) derived from a lymph node metastasis. While the overall frequency of ras gene mutations in prostate tumors is low, when these mutations do occur they may have a role in the progression of disease or the development of the unusual ductal variant of prostatic adenocarcinoma.