ケイラス【KRAS】
読み方：けいらす
⇒ケーラス
ケーラス【KRAS】
読み方：けーらす
《「ケイラス」とも》細胞の増殖に関与する遺伝子の一つ。EGFR（上皮成長因子受容体）が出す細胞増殖のシグナルを受け取り核に伝達する。変異したKRAS遺伝子は、EGFRからのシグナルがなくても、常に細胞増殖のシグナルを出し続ける。膵臓癌(すいぞうがん)・肺癌(はいがん)・直腸癌(ちょくちょうがん)などでKRAS遺伝子の変異が多くみられる。正式名称はv-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog（カーステンラット肉腫ウイルス癌遺伝子ホモログ）。
[補説] 患者のKRAS遺伝子に異常がある場合、EGFRからのシグナル伝達を阻害するセツキシマブなどの薬剤を投与しても、下流のKRAS遺伝子から細胞増殖のシグナルが出続け、腫瘍細胞の増殖を抑制できないため、効果は期待できない。
Kras
名前 クラス
KRAS
出典: フリー百科事典『ウィキペディア（Wikipedia）』 (2020/09/26 02:20 UTC 版)
KRASは、KRAS proto-oncogene, 'GTPアーゼと定義されている。カーステン・ラット肉腫ウイルスがん遺伝子[5] のproto-oncogeneで、"K-ras"遺伝子, "Ki-ras"遺伝子とも呼ばれ, GTPase活性をもつp21 タンパク質として発見された。1983年に、ヒトがん細胞の活性化'KRAS遺伝子と正常細胞のKRAS遺伝子とそれぞれにコードされるタンパク質の配列[6][7]、1985年にヒト染色体上での位置[8] が報告された。
- ^ a b c GRCh38: Ensembl release 89: ENSG00000133703 - Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000030265 - Ensembl, May 2017
- ^ Human PubMed Reference:
- ^ Mouse PubMed Reference:
- ^ Tsuchida N, Ryder T, Ohtsubo E (1982). “Nucleotide sequence of the oncogene encoding p21 transforming protein of Kirsten murine sarcoma virus”. Science 217: 937-939. PMID 6287573.
- ^ Shimizu K, Birnbaum D, Ruley MA, Fasano O, Suard Y, Edlund L, Taparowsky E, Goldfarb M, Wigler M. (1983). “Structure of the Ki-ras gene of the human lung carcinoma cell line Calu-1.”. Nature. 304 (5926): 497-500. PMID 6308465.
- ^ McGrath JP, Capon DJ, Smith DH, Chen EY, Seeburg PH, Goeddel DV, Levinson AD (1983). “Structure and organization of the human Ki-ras proto-oncogene and a related processed pseudogene”. Nature 304 (5926): 501–6. doi:10.1038/304501a0. PMID 6308466.
- ^ Popescu NC, Amsbaugh SC, DiPaolo JA, Tronick SR, Aaronson SA, Swan DC (March 1985). “Chromosomal localization of three human ras genes by in situ molecular hybridization”. Somat. Cell Mol. Genet. 11 (2): 149–55. doi:10.1007/BF01534703. PMID 3856955.
- ^ Kranenburg O (November 2005). “The KRAS oncogene: past, present, and future”. Biochim. Biophys. Acta 1756 (2): 81–2. doi:10.1016/j.bbcan.2005.10.001. PMID 16269215.
- ^ Schubbert S, Zenker M, Rowe SL, et al. (2006). “Germline KRAS mutations cause Noonan syndrome”. Nat. Genet. 38 (3): 331–6. doi:10.1038/ng1748. PMID 16474405.
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- ^ Almoguera C, Shibata D, Forrester K, Martin J, Arnheim N, Perucho M (1988). “Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes”. Cell 53 (4): 549–54. doi:10.1016/0092-8674(88)90571-5. PMID 2453289.
- ^ Tam IY, Chung LP, Suen WS, et al. (2006). “Distinct epidermal growth factor receptor and KRAS mutation patterns in non-small cell lung cancer patients with different tobacco exposure and clinicopathologic features”. Clin. Cancer Res. 12 (5): 1647–53. doi:10.1158/1078-0432.CCR-05-1981. PMID 16533793.
- ^ Vogelstein B, Kinzler KW (2004). “Cancer genes and the pathways they control”. Nat. Med. 10 (8): 789-99. doi:10.1038/nm1087. PMID 15286780.
- ^ Lièvre A, Bachet JB, Le Corre D, et al. (2006). “KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer”. Cancer Res. 66 (8): 3992–5. doi:10.1158/0008-5472.CAN-06-0191. PMID 16618717.
- ^ L. van Epps, PhD, Heather (Winter, 2008). “Bittersweet Gene: A gene called KRAS can predict which colorectal cancers will respond to a certain type of treatment—and which will not.”. CURE (Cancer Updates, Research and Education)
- ^ Bokemeyer C, Bondarenko I, Makhson A, Hartmann JT, Aparicio J, de Braud F, Donea S, Ludwig H, Schuch G, Stroh C, Loos AH, Zubel A, Koralewski P (February 2009). “Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer”. J. Clin. Oncol. 27 (5): 663–71. doi:10.1200/JCO.2008.20.8397. PMID 19114683.
- ^ a b Van Cutsem E, Köhne CH, Hitre E, Zaluski J, Chang Chien CR, Makhson A, D'Haens G, Pintér T, Lim R, Bodoky G, Roh JK, Folprecht G, Ruff P, Stroh C, Tejpar S, Schlichting M, Nippgen J, Rougier P (April 2009). “Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer”. N. Engl. J. Med. 360 (14): 1408–17. doi:10.1056/NEJMoa0805019. PMID 19339720.
- ^ a b Suda K, Tomizawa K, Mitsudomi T (March 2010). “Biological and clinical significance of KRAS mutations in lung cancer: an oncogenic driver that contrasts with EGFR mutation”. Cancer Metastasis Rev. 29 (1): 49–60. doi:10.1007/s10555-010-9209-4. PMID 20108024.
- ^ Riely GJ, Marks J, Pao W (April 2009). “KRAS mutations in non-small cell lung cancer”. Proc Am Thorac Soc 6 (2): 201–5. doi:10.1513/pats.200809-107LC. PMID 19349489.
- ^ Pao W, Wang TY, Riely GJ, Miller VA, Pan Q, Ladanyi M, Zakowski MF, Heelan RT, Kris MG, Varmus HE (January 2005). “KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib”. PLoS Med. 2 (1): e17. doi:10.1371/journal.pmed.0020017. PMC: 545207. PMID 15696205.
- ^ OncoGenetics.Org (2009年7月). “FDA updates Vectibix and Erbitux labels with KRAS testing info”. OncoGenetics.Org. 2009年7月20日閲覧。 [リンク切れ]
- ^ a b Li W, Han M, Guan KL (April 2000). “The leucine-rich repeat protein SUR-8 enhances MAP kinase activation and forms a complex with Ras and Raf”. Genes Dev. 14 (8): 895–900. PMC: 316541. PMID 10783161.
- ^ Kiyono M, Kato J, Kataoka T, Kaziro Y, Satoh T (September 2000). “Stimulation of Ras guanine nucleotide exchange activity of Ras-GRF1/CDC25(Mm) upon tyrosine phosphorylation by the Cdc42-regulated kinase ACK1”. J. Biol. Chem. 275 (38): 29788–93. doi:10.1074/jbc.M001378200. PMID 10882715.
- ^ Rubio I, Wittig U, Meyer C, Heinze R, Kadereit D, Waldmann H, Downward J, Wetzker R (November 1999). “Farnesylation of Ras is important for the interaction with phosphoinositide 3-kinase gamma”. Eur. J. Biochem. 266 (1): 70–82. doi:10.1046/j.1432-1327.1999.00815.x. PMID 10542052.
- ^ Spaargaren M, Bischoff JR (December 1994). “Identification of the guanine nucleotide dissociation stimulator for Ral as a putative effector molecule of R-ras, H-ras, K-ras, and Rap”. Proc. Natl. Acad. Sci. U.S.A. 91 (26): 12609–13. doi:10.1073/pnas.91.26.12609. PMC: 45488. PMID 7809086.
- ^ Vos MD, Ellis CA, Elam C, Ulku AS, Taylor BJ, Clark GJ (July 2003). “RASSF2 is a novel K-Ras-specific effector and potential tumor suppressor”. J. Biol. Chem. 278 (30): 28045–51. doi:10.1074/jbc.M300554200. PMID 12732644.
- ^ NSCLCのKRAS遺伝子変異と増幅が葉酸代謝拮抗薬の効果に関係がある可能性【AACR-NIH-EORTC 2011】 [1]
[続きの解説]
- KRASのページへのリンク
