Disease relevance of ras

• In a more detailed analysis, the v-Ha-ras transfectants OV-ras4 and OV-ras7 were found to form colonies in various organs by metastasis from tumors after s.c. injection, as well as lung colonies after i.v. injection [1].
• These findings suggest that Bin1 loss cooperates with ras activation to drive progression, establishing a role for Bin1 as a negative modifier of oncogenicity and progression in breast cancer [2].
• Experiments were designed to examine the efficacy of IL-2 gene therapy in a surgical minimal residual tumour disease, using moderately immunogenic MK16/1/IIIABC murine cells transformed by activated ras and HPV 16 E6/E7 oncogenes (MK16 cells) [3].
• The ras mutation, which is observed in 20-30% of human nonsmall cell lung cancers (NSCLCs), is one of common genetic alterations and has been proposed to be a prognostic factor in lung cancer [4].
• Human rhabdomyosarcomas (RMSs) frequently demonstrate genetic alterations in ras and p53 [5].

High impact information on ras

• A new study indicates that wildtype Kras2 has properties of a tumor suppressor gene and may have the capacity to reduce the transforming potential of oncogenically activated ras [6].
• BACKGROUND: Point mutations in the ras proto-oncogene that activate its oncogenic potential occur in approximately 30% of human cancers [7].
• BACKGROUND: Activated forms of the ras proto-oncogene have been found in approximately 30% of human malignancies, including pancreatic, colon, and lung adenocarcinomas [8].
• We previously reported that mouse NIH 3T3 cells transformed by transfection of activated human c-Ha-ras become apparently normal upon treatment with the antibiotic azatyrosine [9].
• To address the role of ras signaling in monocytic phagocytes in vivo, the expression of two dominant suppressors of in vitro ras signaling pathways, the carboxyl-terminal region of the GTPase-activating protein (GAP-C) and the DNA binding domain of the transcription factor ets-2, were targeted to this cell compartment [10].

Biological context of ras

• Activations of oncogenes, ras, mos, abl, etc. and mutations in tumor suppressor genes such as p53 were also detected in specific tumors in cancer-prone descendants [11].
• The results indicate that ras action is critical in monocytic cells after these cells have lost the capacity to traverse the cell cycle [10].
• Analysis of the pattern of methylation of specific genes reveals that different types of genes are demethylated in the ras transfectants: skeletal muscle specific genes, a gene specifically expressed in the adrenal cortex (c21), ubiquitous genes, and exogenously introduced sequences [12].
• The regions from -3700 to -220 and +500 to +4400 contributed equally to the ras-mediated inhibition of the parental plasmid [13].
• We conclude that ras transformation suppresses the function of a cell-specific enhancer in the first intron of the alpha 1(I) collagen gene [13].

Anatomical context of ras

• Alterations in differentiation and behavior of monocytic phagocytes in transgenic mice that express dominant suppressors of ras signaling [10].
• We have previously shown that transformation of fibroblasts by ras results in transcriptional inhibition of the alpha 1(I) gene [13].
• A radiation-induced murine ovarian granulosa cell tumor line: introduction of v-ras gene potentiates a high metastatic ability [1].
• Lysyl oxidase (ras recision gene) expression in human amnion: ontogeny and cellular localization [14].
• CD44s (standard isoform) levels and hyaluronan-binding activity were investigated in Balb/c 3T3 cells and their derivatives transformed with ras or sis oncogenes as a function of serum concentration in the medium [15].

Associations of ras with chemical compounds

• Retinoic acid prevents downregulation of ras recision gene/lysyl oxidase early in adipocyte differentiation [16].
• Regulation of p21/ras protein expression by diallyl sulfide in DMBA induced neoplastic changes in mouse skin [17].
• Activation of the lutropin/choriogonadotropin receptor in MA-10 cells stimulates tyrosine kinase cascades that activate ras and the extracellular signal regulated kinases (ERK1/2) [18].

Regulatory relationships of ras

• The full 2 kb murine LOX promoter was very active in 3T6-5 myofibroblast-like cells (MFLC) and vascular smooth muscle cells (SMC) and was inhibited in ras-transformed fibroblasts [19].

Other interactions of ras

• Thus, the lysyl oxidase propeptide, which is released during extracellular proteolytic processing of pro-lysyl oxidase, functions to inhibit ras-dependent cell transformation [20].
• A 43-kDa nuclear IRF-1 protein was expressed biphasically during the cell cycle in primary mouse embryo fibroblasts, nontransformed NIH 3T3 cells, and ras revertants [21].
• These data demonstrate that serum factors, specifically PDGF, mediate regulation of CD44 levels in BAlb/c 3T3 cells and that transformation of 3T3 cells by ras renders CD44 expression insensitive to the modulating effects of serum in vitro [15].
• In PB-3c mastocytes, ionophore-induced IL-3 and GM-CSF expression is primarily the result of mRNA stabilization, and is enhanced by oncogenic ras [22].
• The ras-related GTPase rac1 regulates a proliferative pathway selectively utilized by G-protein coupled receptors [23].

Analytical, diagnostic and therapeutic context of ras

• Persistence, immune specificity, and functional ability of murine mutant ras epitope-specific CD4(+) and CD8(+) T lymphocytes following in vivo adoptive transfer [24].
• Molecular cloning of the cDNA revealed it to be identical to the ras recision gene (rrg), for lysyl oxidase [16].
• The expression level of signal transduction genes; pkC, pdgfr alpha, jak 1, eps 8, tgf beta 1i4, strap and h ras measured by real-time RT-PCR confirmed their expression levels to those obtained from cDNA array [25].
• The expression of activated ras oncogenes was found to be associated with that of tumour-specific transplantation antigens in mouse tumours, which can be cured by adoptive immunotherapy with T lymphocytes and interleukin-2 (IL-2) [26].

References