DOI: 10.3724/SP.J.1264.2011.00020

Chinese Journal of Multiple Organ Diseases in the Elderly (中华老年多器官疾病杂志) 2011/10:4 PP.370-373

RASAL1 expression and ras activity with gastrointestinal tumors: a review

Approximately 20% of human tumors are associated with mutations of ras genes. Ras proteins control cellular signaling pathways responsible for cell proliferation, differentiation, survival and apoptosis. Ras proteins belong to the large family of small GTPases, which are activated in response to various extracellular stimuli. RASAL1, as a ras GTPase activating protein, inhibits ras acti-vation. Regulation of ras and RASAL1 activities may lead the direction of target treatment of tumors. Detection of ras and RASAL1 activities can provide more relevant information about diagnosis and prognosis of gastrointestinal tumors. In this paper, we reviewed the structure, the biochemical properties of ras proteins, and the role of its mutations in tumors. We further discussed the inhibitive effects of RASAL1 on ras activities. Finally, we commented the correlation of ras and RASAL1 with gastrointestinal tumors.

Key words:RASAL1,ras, gene,tumor,diagnosis,prognosis

ReleaseDate:2014-07-21 15:56:26

[1] Colicelli J. Human ras superfamily proteins and related GTPases [J]. Sci STKE 2004, 2004(250): RE13.

[2] Marte BM, Rodriguez-Viciana P, Wennström S, et al. R-ras can activate the phosphoinositide 3-kinase but not the MAP kinase arm of the ras effector pathways[J]. Curr Biol, 1997, 7(1): 63-70.

[3] Repasky GA, Chenette EJ, Der CJ, et al. Renewing the conspiracy theory debate: does Raf function alone to mediate ras oncogenesis [J]? Trends Cell Biol, 2004, 14(11): 639- 647.

[4] Takai Y, Sasaki T, Matozaki T. Small GTP-binding pro-teins[J]. Physiol Rev, 2001, 81(1): 153-208.

[5] Gideon P, John J, Frech M, et al, Mutational and kinetic analyses of the GTPase activating protein (GAP)-p21 interaction: the C-terminal domain of GAP is not sufficient for full activity [J]. Mol Cell Biol, 1992, 12(5): 2050-2056.

[6] Giehl K. Oncogenic ras in tumour progression and metastasis[J]. Biol Chem, 2005, 386(3): 193-205.

[7] Bos JL. ras oncogenes in human cancer: a review[J]. Cancer Res, 1989, 49(17): 4682-4689.

[8] Forrester K, Almoguera C, Han K, et al. Detection of high incidence of K-ras oncogenes during human colon tumorigenesis[J]. Nature, 1987, 327(6120): 298-303.

[9] Almoguera C, Shibata D, Forrester K, et al. Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes[J]. Cell, 1988, 53(4): 549-554.

[10] Rodenhuis S, van de Wetering ML, Mooi WJ, et al. Mutational activation of the K-ras oncogene. A possible pathogenetic factor in adenocarcinoma of the lung[J]. N Engl J Med, 1987, 317(15): 929-935.

[11] Farr CJ, Saiki RK, Erlich HA, et al. Analysis of ras gene mutations in acute myeloid leukemia by polymerase chain reaction and oligonucleotide probes[J]. Proc Natl Acad Sci U S A, 1988, 85(5): 1629-1633.

[12] Tada M, Yokosuka O, Omata M, et al. Analysis of ras gene mutations in biliary and pancreatic tumors by polymerase chain reaction and direct sequencing[J]. Cancer, 1990, 66(5): 930-935.

[13] Karnoub AE, Weinberg RA. Ras oncogenes: split persona- lities[J]. Nat Rev Mol Cell Biol, 2008, 9(7): 517-531.

[14] Yashiro M, Nishioka N, Hirakawa K. K-ras mutation influences macroscopic features of gastric carcinoma[J]. J Surg Res, 2005, 124(1): 74-78.

[15] Guerrero S, Casanoval I, Farre L, et al . K-ras codon 12 mutation induces higher level of resistance to apoptosis and predisposition to anchorage-independent growth than codon 13 mutation or proto-oncogene overexpression[J]. Cancer Res, 2000, 60(23): 6750-6756.

[16] Glennon TM, Villà J, Warshel A. How does GAP catalyze the GTPase reaction of ras? A computer simulation study[J]. Biochemistry, 2000, 39(32): 9641-9651.

[17] Ahmadian MR, Zor T, Vogt D, et al. Guanosine triphosphatase stimulation of oncogenic ras mutants[J]. Proc Natl Acad Sci U S A, 1999, 96(12): 7065-7070.

[18] Kosloff M, Selinger Z. Substrate assisted catalysis— application to G proteins[J]. Trends Biochem Sci, 2001, 26(3): 161-166.

[19] Walker SA, Kupzig S, Bouyoucef D, et al. Identifi-cation of a ras GTPase-activating protein regulated by re-ceptor- mediated Ca2+ oscillations [J]. EMBO J, 2004, 23(8): 1749- 1760.

[20] Liu Q, Walker SA, Gao D, et al. CAPRI and rasAL impose different modes of information processing on ras due to contrasting temporal filtering of Ca2+[J].J Cell Biol, 2005, 170(2): 183-190.

[21] Kolfschoten IG, van Leeuwen B, Berns K, et al. A genetic screen identifies pitx1 as a suppressor of ras activity and tumorigenicity[J]. Cell, 2005, 121(6): 849-858.

[22] Ohta M, Seto M, Ijichi H, et al. Decreased expression of the ras-GTPase activating protein RASAL1 is associated with colorectal tumor progression[J]. Gastroenterology, 2009, 136(1): 206-216.

[23] Li M, Liu W, Zhu YF, et al. Correlation of COX-2 and K-ras expression to clinical outcome in gastric cancer[J]. Acta Oncol, 2006, 45(8): 1115-1119.

[24] Yamamoto H, Itoh F, Senota A, et al . Expression of matrix metalloproteinase matrilysin (MMP-7) was induced by activated K-ras via AP-1 activation in SW1417 colon cancer cells[J]. J Clin Lab Anal. 1995, 9(5): 297-301.

[25] Hiyama T, Haruma K, Kitadai Y, et al. K-ras mutation in helicobacter pylori-associated chronic gastritis in patients with and without gastric cancer[J]. Int J Cancer, 2002, 97(5): 562-566.

[26] Hiyama T, Tanaka S, Haruma K, et al. The roles of H. pylori infection and K-ras gene mutation in gastric carcinogenesis[J]. Nippon Rinsho, 2003, 61(1): 46-49.

[27] Gjertsen MK, Gaudernack G. Mutated ras peptides as vaccines in immunotherapy of cancer[J]. Vox Sang, 1998, 74Suppl 2: 489-495.

[28] Fossum B, Olsen AC, Thorsby E, et al. CD8+ T cells from a patient with colon carcinoma, specific for a mutant p21-rasderived peptide (Gly13YAsp), are cytotoxic towards a carcinoma, cell line harbouring the same mutation[J]. Cancer Immunol Immunother, 1995, 40(3): 165-172.

[29] Gjertsen MK, Buanes T, Rosseland AR, et al. In-tradermal ras peptide vaccination with granulo-cyte-macrophage colony stimulating factor as adjuvant: Clinical and immunological responses in patients with pancre-atic adenocarcinoma[J]. Int J Cancer, 2001, 92(3): 441- 450.

[30] Khleif SN, Abrams SI, Hamilton JM, et al. A phase I vaccine trial with peptides reflecting ras oncogene muta-tions of solid tumors[J]. J Immunother, 1999, 22(2): 155-165.