Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.27.5 (RNase)
 17,967 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pheochromocytomas occur sporadically or in individuals affected by inherited syndromes including multiple endocrine neoplasia (MEN) type 2A and 2B, neurofibromatosis, and the von Hippel-Lindau syndrome (vHL). Medullary thyroid carcinomas (MTCs) also occur sporadically or as part of MEN 2A, MEN 2B, and familial MTC. Little is known of the molecular genetic background of these tumors. We have shown previously that activation of the N-ras, H-ras, and K-ras oncogenes does not occur in these tumors, but that deletions of the short arm of chromosome 1 are extremely common (> 60%) and may indicate loss of a suppressor gene in the chromosomal region 1p31-36. We have examined the structure and expression of N-myc, c-myc, L-myc, c-mos, nerve growth factor (beta-NGF), and the low affinity nerve growth factor receptor (LNGFR) in a series of pheochromocytomas and MTCs from patients with hereditary and sporadic diseases. Southern analysis, using radiolabeled DNA probes, revealed no evidence of amplification or rearrangement of these genes in any normal or tumor tissues except for loss of heterozygosity at the L-myc locus (1p32) in 9 pheochromocytomas from patients with MEN 2A or MEN 2B, in 5 of 11 non-MEN pheochromocytomas, and in 3 of 24 non-MEN MTCs. Gene expression at the RNA level was examined by Northern analysis or ribonuclease protection assay (RPA) using radiolabeled DNA or cRNA probes. C-myc transcripts were detectable at low levels in all tumors tested.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oncogene and growth factor expression in MEN 2 and related tumors. 136 25

The presence of point mutations in the K-ras gene was examined in murine thymic lymphomas induced by a single dose of N-methylnitrosourea by the RNase A mismatch cleavage method and by allelic-specific oligonucleotide hybridization of in vitro amplified DNA by polymerase chain reaction. The results show that the frequency of mutations is lower than that of tumors induced by multiple N-methylnitrosourea treatments. Four mutations identified were the aspartic acid at codon 12, a G:C to A:T transition in its second position. A G:C to T:A transversion in codon 146 was also found in one thymic lymphoma, changing the amino acid alanine to serine. The use of the RNase A assay allowed an estimation of the relative expression levels of both normal and mutant K-ras alleles. The results show that in approximately one half of the tumors the mutant allele is predominantly expressed, suggesting that the normal allele has been lost or that the mutant allele has been amplified relative to the normal. Altogether, these findings are consistent with ras mutations occurring in some instances during tumor development and with a ras effect being not strictly dominant but favoring selection for increasing levels of expression from the oncogenic allele.
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PMID:Differential expression of the normal and mutated K-ras alleles in chemically induced thymic lymphomas. 171 39

Pancreatic ductal adenocarcinomas induced in the Syrian golden hamster (SGH) by N-nitrosobis(2-oxopropyl)amine share many similarities with the human disease, including mutations of the K-ras oncogene. In vitro carcinogenesis studies with immortal SGH pancreatic duct cells indicate that neoplastic transformation in this system can occur without mutational inactivation of p53 suppressor gene. In this study we extend the genetic analysis of the in vivo SGH model to increase the number of cases analyzed for the status of K-ras and to determine further the spectrum of alterations involved; we have studied the status of the p53, DCC, and Rb-1 suppressor genes and the status of the mdm2 oncogene, which can involve p53 indirectly. The partial SGH-coding sequence of mdm2 and DCC was determined. K-ras mutation in the second position of codon 12 was present in 17 of 19 (90%) of tumors. Immunohistochemistry and single strand conformation polymorphism analysis showed no evidence of p53 mutation in 21 tumors. RNase protection assays showed overexpression of mdm2 in 5 of 19 (26%) tumors. Semiquantitative reverse transcription-PCR analysis showed a complete or partial loss of DCC expression in 10 of 19 (53%) neoplasms and of Rb-1 (42%) expression in 8 of 19 tumors when compared to matched controls. Deregulation of these genes appears to be significant in SGH pancreatic carcinogenesis as indicated by their frequencies. However, the fact that 6 tumors showed either only a K-ras mutation or the absence of alterations of the 5 genes analyzed indicates that additional as yet unstudied or unknown genes are also involved in SGH pancreatic duct carcinogenesis.
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PMID:Multiple genetic alterations in hamster pancreatic ductal adenocarcinomas. 778 Sep 69

Current histopathological evidence suggests that gall-bladder cancer has two main morphological pathways for its development: de novo (ab initio) origin and adenoma-carcinoma sequence. In order to investigate the genetic difference between them, APC mutations were examined by RNase protection analysis, K-ras mutations by nested polymerase chain reaction-restriction fragment length polymorphism analysis, and p53 gene overexpression by immunohisto-chemical analysis in both tumors and benign lesions of the gall-bladder. Overexpression of the p53 gene was detected in 105 of 164 (64%) de novo carcinomas regardless of size and depth of invasion, but not in 16 tumors of carcinoma-in-pyloric-gland-type adenoma, or in 51 adenomas (47 pyloric gland-type and 4 intestinal-type). K-ras codon 12 mutation was detected in 4 of 40 (10%) de novo carcinomas, all four being associated with p53 gene overexpression, but not in 12 tumors of carcinoma in adenoma or 16 adenomas (14 pyloric gland-type and 2 intestinal-type). APC mutation was not found in 16 de novo carcinomas or the one pyloric gland-type adenoma examined. These results suggest that there are two distinct genetic pathways in gall-bladder carcinogenesis; that is, de novo carcinoma develops from a predominant p53 alteration with low K-ras mutation, and carcinoma-in-pyloric-gland-type adenoma develops from p53-, K-ras-, and APC-gene-unrelated, as yet unknown, alteration.
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PMID:APC, K-ras codon 12 mutations and p53 gene expression in carcinoma and adenoma of the gall-bladder suggest two genetic pathways in gall-bladder carcinogenesis. 880 79

Recent studies have suggested that cholecystokinin (CCK) receptors may play a role in the development and growth of pancreatic cancers. We detected the expression of mRNA encoding CCK-A and CCK-B receptors in eight human pancreatic tumour cell lines using reverse transcription-polymerase chain reaction (RT-PCR), but not by RNase protection assays. The K-ras gene, which can be activated by G-coupled protein receptors such as CCK receptors, was mutated in codon 12 in five of the cell lines. In addition, Mia PaCa-2 pancreatic cancer cells did not respond to CCK or gastrin in cell proliferation or focal adhesion kinase (FAK) phosphorylation assays. In contrast, mouse NIH3T3 fibroblasts transfected with human CCK-B receptor (NIH3T3CCK-BR) showed increased proliferation and phosphorylation to the peptides. Also, radioligand binding studies indicated that Mia PaCa-2 cells had approximately 12.5-fold less CCK-B receptors than NIH3T3CCK-BR. Our results suggest that in Mia PaCa-2 cells, CCK receptors may not play a crucial role in supporting cell growth.
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PMID:Cholecystokinin receptors in human pancreatic cancer cell lines. 984 31

Approximately 15-30% of human non-small cell lung cancers (NSCLC) carry K-ras mutations, among which point mutations at codon 12 are the most common. This study characterizes the anti-tumor effect of an anti-K-ras ribozyme adenoviral vector (KRbz-ADV; replication-deficient, E1-deleted Ad5 backbone) against NSCLC lines that express the relevant mutation (K-ras codon 12 GGT --> GTT; H441 and H1725). KRbz-ADV significantly inhibited tumor cell growth (38-94% reduction by 3H-thymidine uptake) in a time- and dose-dependent manner, but produced minimal growth inhibition on normal epithelial cells, or NSCLC H1650 cells that lack the relevant mutation. The in vivo anti-tumorigenic effect of KRbz-ADV treatment was characterized with cell line xenografts in nu/nu mice. Pre-treatment with KRbz-ADV (10 or 20 p.f.u. per cell) completely abrogated subcutaneous engraftment of H441 (n = 13) or H1725 cells (n = 8), as compared with a 100% tumor take and progressive tumor growth in animals that received untreated tumor cells, or control vector (luciferase-adenovirus/Luc-ADV)-treated tumor cells. Pre-treatment with a mutant anti-K-ras ribozyme adenoviral vector (mutKRbz-ADV), which has the same specificity as KRbz but lacks ribozyme catalytic activity, did not produce an anti-tumorigenic effect. The in vivo effect of KRbz-ADV treatment was further examined by initiating injections (2 x 10(9) p.f.u.) at 7 days after tumor induction. Pre-existing tumor growth was reduced by 39% by a single intratumoral injection. Repeat injections (three or five KRbz-ADV-intratumoral injections at 2 x 10(9) p.f.u. every other day) resulted in complete tumor regression in five of seven mice. In contrast, single or multiple injections of control vector Luc-ADV did not significantly alter tumor xenograft outcome. Ribozyme expression was confirmed in H441 cells that demonstrated reduced growth after KRbz-ADV treatment. Reduced growth corresponded to significantly lowered levels of K-ras mRNA, as defined by RT-PCR (51% of untreated level, n = 3) and RNase protection assay (56% of untreated level, n = 4) analyses. Further, 37.5% of KRbz-ADV-treated cells underwent apoptosis, as compared with 11.7%, and 19.0% in untreated and Luc-ADV-treated cultures, respectively. A significantly higher proportion of KRbz-ADV-treated H441 cells (58.2%) underwent apoptosis when maintained under anchor-independent conditions that simulate in vivo tumorigenesis ('anoikis'). This is the first report that demonstrates that KRbz-ADV can effectively inhibit in vivo tumorigenesis, and produces regression of pre-existing human lung tumor xenografts having the relevant K-ras mutation.
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PMID:Anti-tumorigenic effect of a K-ras ribozyme against human lung cancer cell line heterotransplants in nude mice. 1117 17