Met proto-oncogene product is overexpressed in tumors of p53-deficient mice and tumors of Li-Fraumeni patients - PubMed

Affiliations

• PMID: 7728766

Met proto-oncogene product is overexpressed in tumors of p53-deficient mice and tumors of Li-Fraumeni patients

S Rong et al. Cancer Res. 1995.

Abstract

Inappropriate expression of Met, the receptor for hepatocyte growth factor/scatter factor, has been implicated in sarcomagenesis via an autocrine mechanism. Sarcomas occur at high frequency in individuals with Li-Fraumeni syndrome as well as in p53-deficient mice. Here we show that these tumors express high levels of Met. Moreover, late passage fibroblast cell lines established from p53-deficient animals overexpress Met and can be tumorigenic in athymic nude mice, suggesting that progression occurs in vitro. The tumor explants display increased hepatocyte growth factor/scatter factor expression and Met turnover, indicating that autocrine Met activation contributes to tumor progression. Thus, the loss of wild-type p53 appears to greatly enhance the opportunity for inappropriate Met expression. Loss of p53 function does not by itself cause transformation, but inappropriate Met expression may be an important factor in sarcomagenesis.

Similar articles

• Tumorigenesis induced by coexpression of human hepatocyte growth factor and the human met protooncogene leads to high levels of expression of the ligand and receptor.

  Rong S, Oskarsson M, Faletto D, Tsarfaty I, Resau JH, Nakamura T, Rosen E, Hopkins RF 3rd, Vande Woude GF. Rong S, et al. Cell Growth Differ. 1993 Jul;4(7):563-9. Cell Growth Differ. 1993. PMID: 8398896

• Scatter factor stimulates tumor growth and tumor angiogenesis in human breast cancers in the mammary fat pads of nude mice.

  Lamszus K, Jin L, Fuchs A, Shi E, Chowdhury S, Yao Y, Polverini PJ, Laterra J, Goldberg ID, Rosen EM. Lamszus K, et al. Lab Invest. 1997 Mar;76(3):339-53. Lab Invest. 1997. PMID: 9121117

• The Met-HGF/SF autocrine signaling mechanism is involved in sarcomagenesis.

  Cortner J, Vande Woude GF, Rong S. Cortner J, et al. EXS. 1995;74:89-121. doi: 10.1007/978-3-0348-9070-0_6. EXS. 1995. PMID: 8527903 Review.

• Li-Fraumeni syndrome: a p53 family affair.

  Iwakuma T, Lozano G, Flores ER. Iwakuma T, et al. Cell Cycle. 2005 Jul;4(7):865-7. doi: 10.4161/cc.4.7.1800. Epub 2005 Jul 4. Cell Cycle. 2005. PMID: 15917654 Review.

Cited by

• A common p53 mutation (R175H) activates c-Met receptor tyrosine kinase to enhance tumor cell invasion.

  Grugan KD, Vega ME, Wong GS, Diehl JA, Bass AJ, Wong KK, Nakagawa H, Rustgi AK. Grugan KD, et al. Cancer Biol Ther. 2013 Sep;14(9):853-9. doi: 10.4161/cbt.25406. Epub 2013 Jun 18. Cancer Biol Ther. 2013. PMID: 23792586 Free PMC article.

• The HGF receptor c-Met is overexpressed in esophageal adenocarcinoma.

  Herrera LJ, El-Hefnawy T, Queiroz de Oliveira PE, Raja S, Finkelstein S, Gooding W, Luketich JD, Godfrey TE, Hughes SJ. Herrera LJ, et al. Neoplasia. 2005 Jan;7(1):75-84. doi: 10.1593/neo.04367. Neoplasia. 2005. PMID: 15720819 Free PMC article.

• Induction of c-met proto-oncogene expression at the metastatic site.

  Imai J, Watanabe M, Sasaki M, Yamaguchi R, Tateyama S, Sugano S. Imai J, et al. Clin Exp Metastasis. 1999 Jul;17(5):457-62. doi: 10.1023/a:1006659515706. Clin Exp Metastasis. 1999. PMID: 10651314

• Expression of Met/hepatocyte growth factor receptor gene and malignant behavior of musculoskeletal tumors.

  Scotlandi K, Baldini N, Oliviero M, Di Renzo MF, Martano M, Serra M, Manara MC, Comoglio PM, Ferracini R. Scotlandi K, et al. Am J Pathol. 1996 Oct;149(4):1209-19. Am J Pathol. 1996. PMID: 8863670 Free PMC article.

• p53 in cell invasion, podosomes, and invadopodia.

  Mak AS. Mak AS. Cell Adh Migr. 2014;8(3):205-14. doi: 10.4161/cam.27841. Cell Adh Migr. 2014. PMID: 24714032 Free PMC article. Review.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Other Literature Sources

  • The Lens - Patent Citations Database

• Molecular Biology Databases

  • Mouse Genome Informatics (MGI)

• Research Materials

  • NCI CPTC Antibody Characterization Program

• Miscellaneous

  • NCI CPTAC Assay Portal