Gumerlock P H, Poonamallee U R, Meyers F J, deVere White R W
Department of Internal Medicine, University of California Davis School of Medicine Sacramento 95817.
Cancer Res. 1991 Mar 15;51(6):1632-7.
Although oncogenically activated ras alleles are common in some types of human cancers, the frequency in human carcinoma of the prostate (CaP) has not previously been addressed. In this paper, we report a comprehensive screening of 19 CaPs and 3 CaP cell lines for activating point mutations in the sequences of the 12th and 61st codons of c-Ha-ras-1 and the c-Ki-ras-2 genes, as well as the 12th, 13th, and 61st codons of the c-N-ras gene. The 19 CaPs were chosen to represent a wide range of stages (B through D), Gleason scores (3 through 10), and DNA ploidy (diploid with low proliferation to nontetraploid-aneuploid). Fifteen of the tumors had been untreated prior to resection and 4 were obtained postradiation therapy. The polymerase chain reaction was used to amplify genomic DNA sequences and transcribed mRNA sequences of the ras genes prior to allele-specific oligonucleotide probe hybridization. We have detected a mutant allele with a point mutation in the second nucleotide of the 61st codon of the c-Ha-ras-1 gene in one specimen. Thus, we conclude that the activation of ras alleles is not significant in the development or progression of most CaPs.
虽然致癌激活的ras等位基因在某些类型的人类癌症中很常见,但此前尚未涉及前列腺癌(CaP)中的频率。在本文中,我们报告了对19例CaP和3种CaP细胞系进行的全面筛查,以检测c-Ha-ras-1和c-Ki-ras-2基因第12和61密码子序列以及c-N-ras基因第12、13和61密码子序列中的激活点突变。选择这19例CaP代表广泛的分期(B期至D期)、Gleason评分(3至10分)和DNA倍体情况(从低增殖的二倍体到非四倍体-非整倍体)。其中15例肿瘤在切除前未接受过治疗,4例是在放射治疗后获得的。在等位基因特异性寡核苷酸探针杂交之前,使用聚合酶链反应扩增ras基因的基因组DNA序列和转录的mRNA序列。我们在一个标本中检测到c-Ha-ras-1基因第61密码子第二个核苷酸发生点突变的突变等位基因。因此,我们得出结论,ras等位基因的激活在大多数CaP的发生或进展中并不显著。