ras GENES

Amplification of Ki-ras and elevation of MAP kinase activity during mammary tumor progression in C3(1)/SV40 Tag transgenic mice

“…The most frequently activated Ras oncogene is Ki-ras with a point mutation in codon 12 or 61. Although Ras mutations are not very common in human breast cancer (Garcia et al, 1989;Prosperi et al, 1990;Theillet et al, 1986), they have been strongly implicated in the etiology of mammary adenocarcinoma in many rat carcinogenesis studies (Barbacid, 1987). Our screen for Ras family gene mutations by PCR ± SSCP detected no mutations for Ki-ras and low levels (9%) of Ha-ras mutations at codon 12.…”

“…The fact that ErbB2/neu/HER2 and c-myc ampli®cations are not observed in this animal model, but are relatively frequent in human breast cancer (Blackwell et al, 1990;Seshadri et al, 1993;Slamon et al, 1989;Varley et al, 1987), suggests that alternate genetic pathways may be involved in Tag-induced mammary cancer progression in mice. Our results showing that Ki-ras is signi®cantly ampli®ed during mammary gland tumor progression in C3(1)/SV40 Tag transgenic mice, together with the demonstration by others of the important role of Ha-ras gene alterations during rat mammary oncogenesis (Barbacid, 1987) 0/32 0/32 a Ha-ras and Ki-ras mutations were examined in mammary tumors by SSCP as described in Materials and methods. Results are expressed as the number of mutated tumors in total samples examined suggest that perturbations in ras gene family members may be more frequently involved in rodent than human mammary tumorigenesis.…”

“…It is estimated that Ras mutations are present in 10 ± 15% of the most common forms of human neoplasia (Barbacid, 1987), including 90% of pancreatic adenocarcinomas, 50% of colon carcinomas and 20% of lung carcinomas. Ras activation mutations frequently result from single point mutations at amino acid 12 or 61 (Capon et al, 1983).…”

Transformation by ras modifies AP1 composition and activity

“…These proto-oncogenes, frequently mutated in human tumors, connect receptors as the cell membrane with a cytoplasmic cascade of protein kinases followed by downstream nuclear events including induction of transcription and DNA synthesis. The proteins (p21Ras) encoded by the ras genes (Harvey-ras/Ha-ras, Kirsten-ras/Ki-ras and N-ras) bind guanine nucleotides, possess an intrinsic GTPase activity and cycle between an active (GTP bound) form and an inactive (GDP bound) state (Barbacid, 1987). Activated p21Ras proteins stimulate a cascade of cytoplasmic protein kinases including Raf, MEK, MAPK (Mitogen Activated Protein Kinase) which in turn culminates in the phosphorylation of nuclear transcription factors resulting in transcriptional activation of growth-mediating genes (Bollag and McCormick, 1991;Boulton et al, 1991;de Vries-Smit et al, 1992;Dent et al, 1992;De rijard et al, 1994;Hibi et al, 1993;Howe et al, 1992;Kyriakis et al, 1992;Lowenstein et al, 1992;Wood et al, 1992).…”

Developmentally-regulated expression of murine K-ras isoforms

“…Genes of the highly conserved ras family encode small (21 kDa) guanine nucleotide-binding proteins which are involved in the regulation of proliferation and di erentiation (Barbacid, 1987;Lowy and Willumsen, 1993). Mammals express three ras genes, designated H-, N-and K-ras.…”