Disease relevance of Genes, ras

• The first, a benign hyperplasia of the Harderian lacrimal gland, is diffuse, involves the entire gland, and likely requires only the abnormal action of the v-Ha-ras gene [1].
• Loss of ras oncogene mutation in a myelodysplastic syndrome after low-dose cytarabine therapy [2].
• A combination of DNA hybridization analyses and tissue sectioning techniques demonstrate that ras gene mutations occur in over a third of human colorectal cancers, that most of the mutations are at codon 12 of the c-Ki-ras gene and that the mutations usually precede the development of malignancy [3].
• Over 90% of tumours, including premalignant papillomas, initiated with dimethylbenzanthracene (DMBA) have a specific A----T transversion at the second nucleotide of codon 61 of the Harvey-ras (Ha-ras) gene [4].
• We have now used monoclonal antibodies directed against a synthetic peptide reflecting sequences of the human T24 ras gene product to define ras p21 protein expression in a spectrum of colonic disease states [5].

Psychiatry related information on Genes, ras

• Genetic studies have attempted to link (bipolar) affective disorder to the short arm of chromosome 11 (where the loci for insulin, insulin growth factor (IGF), tyrosine hydroxylase (TH) and h-ras-oncogene are located) but these have failed [6].

High impact information on Genes, ras

• The 3'UTRs of the human RAS genes contain multiple LCSs, allowing let-7 to regulate RAS expression. let-7 expression is lower in lung tumors than in normal lung tissue, while RAS protein is significantly higher in lung tumors, providing a possible mechanism for let-7 in cancer [7].
• By screening for mutations that suppress the vulval defects caused by a constitutively active let-60 ras gene, we identified six loss-of-function alleles of ksr-1, a novel C. elegans gene [8].
• Using a reconstituted mouse prostate organ, the effects on endogenous p53 expression of the ras oncogene or of the ras + myc oncogenes were investigated [9].
• The rap1/Krev-1 gene encodes a ras-related protein that suppresses transformation by ras oncogenes [10].
• For example, the human H-ras gene can substitute for yeast RAS; the relationship is sufficiently close that dominant Ha-ras mutations that inhibit CDC25 have been found (Powers et al., 1989) [11].

Chemical compound and disease context of Genes, ras

• To investigate the role of an activated K-Ras gene in the initiation and maintenance of lung adenocarcinomas, we developed transgenic mice that express murine K-Ras4b(G12D) under the control of doxycycline in type II pneumocytes [12].
• Activation of growth factor secretion in tumorigenic states of breast cancer induced by 17 beta-estradiol or v-Ha-ras oncogene [13].
• Primary granulosa cells were prepared from diethylstilbestrol-treated immature female rats and transfected with simian virus 40 (SV40) DNA or with SV40 plus activated human Ha-RAS oncogene [14].
• Reduction in the frequency of activated ras oncogenes in rat mammary carcinomas with increasing N-methyl-N-nitrosourea doses or increasing prolactin levels [15].
• In addition, 14 formalin-fixed and paraffin-embedded rat esophageal papillomas were shown to contain the same mutation in one of the alleles of the Ha-ras gene [16].

Biological context of Genes, ras

• This evidence suggests that NF1 encodes a cytoplasmic GAP-like protein that may be involved in the control of cell growth by interacting with proteins such as the RAS gene product [17].
• Recent studies have demonstrated that the cellular tumour antigen p53 (ref. 1) can complement activated ras genes in the transformation of rat fibroblasts, suggesting that the gene encoding p53 may act as an oncogene [18].
• Transfection studies show that the p53 gene, in collaboration with the activated ras oncogene, can transform cells [19].
• Harvey (Ha-MSV) and Kirsten (Ki-MSV) murine sarcoma viruses induce tumours in animals and transform various cells in culture because of the expression of the ras oncogene product, p21 (ref. 1). Proto-oncogenes homologous with these genes are highly conserved evolutionarily and activated ras oncogenes have been detected in many human cancers [20].
• We propose that recA protein may change its conformation upon ATP hydrolysis in a manner analogous to one such protein, the p21 protein from the ras oncogene [21].

Anatomical context of Genes, ras

• The v-erbB, v-src, v-fps, v-sea, and v-Ha-ras oncogenes induce avian erythroid progenitor cells to self-renew in an erythropoietin-independent manner [22].
• Cysteine is encoded at the twelfth amino acid position, suggesting that the Calu-1 Ki-ras gene has undergone a mutational activation at the same position as the human Ha-ras gene of the bladder carcinoma cell line, T24 [23].
• Analysis of rat fibroblasts transfected with these altered genes demonstrates that all amino acids except glycine (which is encoded by normal cellular ras genes) and proline at position 12 activate p21, suggesting a requirement for an alpha-helical structure in this region of the polypeptide [24].
• The let-60 gene, an essential ras gene of the nematode Caenorhabditis elegans, acts as a switch in the inductive signalling pathway that initiates vulva formation [25].
• ras Oncogene p21 antigen is present in the most superficial cells of the normal bladder urothelium, as demonstrated by immunohistochemical staining [26].

Associations of Genes, ras with chemical compounds

• These results indicate that structural mutations which activate ras gene transforming activity do not alter the protein's known biochemical parameters and in particular do not affect the protein's intrinsic ability to bind guanine nucleotides [27].
• Vulval differentiation in Caenorhabditis elegans is controlled by intercellular signalling mediated by a receptor tyrosine kinase and a ras gene product [28].
• We demonstrate a reproducible increase in 1,2-diacylglycerol, in the absence of a detectable increase in inositol phosphates, in transformed cells containing Ha-ras oncogenes and with different membrane targeting signals for the ras p21 protein [29].
• One of the most commonly found transforming ras oncogenes in human tumours has a valine codon replacing the glycine codon at position 12 of the normal c-Ha-ras gene [30].
• Novel source of 1,2-diacylglycerol elevated in cells transformed by Ha-ras oncogene [29].

Gene context of Genes, ras

• In these experiments we demonstrate that purified RAS proteins, whether derived from the yeast RAS1 or RAS2 or the human H-ras genes, activate yeast adenylate cyclase in the presence of guanine nucleotides [31].
• We have cloned the let-60 gene, and shown that it encodes a gene product identical in 84% of its first 164 amino acids to ras gene products from other vertebrate and invertebrate species [32].
• We have identified a gene, SRV2, mutations of which alleviate stress sensitivity in strains carrying an activated RAS gene [33].
• The yeast Saccharomyces cerevisiae contains two functional homologues of the ras oncogene family, RAS1 and RAS2 [34].
• Two C. elegans MAP kinase genes, mpk-1 and mpk-2 (mpk, MAP kinase), were cloned using degenerate oligonucleotide primers and PCR amplification; in parallel, genes involved in vulval induction were identified by screening for mutations that suppress the vulval defects caused by an activated let-60 ras gene [35].

Analytical, diagnostic and therapeutic context of Genes, ras

• In a cell culture model of this phenomenon, we have previously demonstrated that insertion of the viral Harvey ras gene (v-Ha-ras) into SCLC cell lines with amplification and overexpression of the c-myc gene induced many NSCLC phenotypic features [36].
• Using patch-clamp techniques, we find that agents activating PKC, including phorbol esters and a ras oncogene product (p21) that induces neurites, caused little increase in channel number [37].
• Expression of the c-myc gene was localized to nuclei and reached a maximum at 3 h, and that of the c-Ha-ras gene was localized to cytoplasm with a peak at 6-12 h after treatment on the mucous neck, parietal, chief, and enterochromaffinlike cells around the lesions [38].
• In six independently derived rat cell lines transformed by a murine cDNA-genomic hybrid clone of p53 plus an activated Ha-ras gene, elevated levels of p53 were detected by immunoprecipitation by using murine-specific anti-p53 monoclonal antibodies [39].
• Cellular ras oncogene expression and cell cycle measured by flow cytometry in hematopoietic cell lines [40].

References