Transgenic expression of tpr-met oncogene leads to development of mammary hyperplasia and tumors (original) (raw)

Abstract

Receptor tyrosine kinases are important in cell signal transduction and proliferation. Abnormal expression of tyrosine kinases often leads to malignant transformation. C-met is a tyrosine kinase receptor and its ligand is hepatocyte growth factor (HGF). HGF/c-met plays diverse role in regulation of cell growth, shape and movement. Constitutively activated met, such as tpr-met, is a potent oncogene in vitro, but its carcinogenic role in vivo remains unclear. Our study demonstrates that expression of tpr-met leads to development of mammary tumors and other malignancies in transgenic mice, and suggests that deregulated met expression may be involved in mammary carcinogenesis.

Full Text

The Full Text of this article is available as a PDF (577.8 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bargmann C. I., Hung M. C., Weinberg R. A. Multiple independent activations of the neu oncogene by a point mutation altering the transmembrane domain of p185. Cell. 1986 Jun 6;45(5):649–657. doi: 10.1016/0092-8674(86)90779-8. [DOI] [PubMed] [Google Scholar]
  2. Bièche I., Champème M. H., Matifas F., Hacène K., Callahan R., Lidereau R. Loss of heterozygosity on chromosome 7q and aggressive primary breast cancer. Lancet. 1992 Jan 18;339(8786):139–143. doi: 10.1016/0140-6736(92)90208-k. [DOI] [PubMed] [Google Scholar]
  3. Bottaro D. P., Rubin J. S., Faletto D. L., Chan A. M., Kmiecik T. E., Vande Woude G. F., Aaronson S. A. Identification of the hepatocyte growth factor receptor as the c-met proto-oncogene product. Science. 1991 Feb 15;251(4995):802–804. doi: 10.1126/science.1846706. [DOI] [PubMed] [Google Scholar]
  4. Capetanaki Y., Kuisk I., Rothblum K., Starnes S. Mouse vimentin: structural relationship to fos, jun, CREB and tpr. Oncogene. 1990 May;5(5):645–655. [PubMed] [Google Scholar]
  5. Cardiff R. D., Sinn E., Muller W., Leder P. Transgenic oncogene mice. Tumor phenotype predicts genotype. Am J Pathol. 1991 Sep;139(3):495–501. [PMC free article] [PubMed] [Google Scholar]
  6. Chan A. M., King H. W., Tempest P. R., Deakin E. A., Cooper C. S., Brookes P. Primary structure of the met protein tyrosine kinase domain. Oncogene. 1987 May;1(2):229–233. [PubMed] [Google Scholar]
  7. Comoglio P. M. Structure, biosynthesis and biochemical properties of the HGF receptor in normal and malignant cells. EXS. 1993;65:131–165. [PubMed] [Google Scholar]
  8. Di Renzo M. F., Narsimhan R. P., Olivero M., Bretti S., Giordano S., Medico E., Gaglia P., Zara P., Comoglio P. M. Expression of the Met/HGF receptor in normal and neoplastic human tissues. Oncogene. 1991 Nov;6(11):1997–2003. [PubMed] [Google Scholar]
  9. Faletto D. L., Kaplan D. R., Halverson D. O., Rosen E. M., Vande Woude G. F. Signal transduction in c-met mediated motogenesis. EXS. 1993;65:107–130. [PubMed] [Google Scholar]
  10. Gherardi E., Stoker M. Hepatocyte growth factor--scatter factor: mitogen, motogen, and met. Cancer Cells. 1991 Jun;3(6):227–232. [PubMed] [Google Scholar]
  11. Grigioni W. F., Fiorentino M., D'Errico A., Ponzetto A., Crepaldi T., Prat M., Comoglio P. M. Overexpression of c-met protooncogene product and raised Ki67 index in hepatocellular carcinomas with respect to benign liver conditions. Hepatology. 1995 Jun;21(6):1543–1546. [PubMed] [Google Scholar]
  12. Huang M. T., Gorman C. M. The simian virus 40 small-t intron, present in many common expression vectors, leads to aberrant splicing. Mol Cell Biol. 1990 Apr;10(4):1805–1810. doi: 10.1128/mcb.10.4.1805. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Landschulz W. H., Johnson P. F., McKnight S. L. The leucine zipper: a hypothetical structure common to a new class of DNA binding proteins. Science. 1988 Jun 24;240(4860):1759–1764. doi: 10.1126/science.3289117. [DOI] [PubMed] [Google Scholar]
  14. Low M. J., Hammer R. E., Goodman R. H., Habener J. F., Palmiter R. D., Brinster R. L. Tissue-specific posttranslational processing of pre-prosomatostatin encoded by a metallothionein-somatostatin fusion gene in transgenic mice. Cell. 1985 May;41(1):211–219. doi: 10.1016/0092-8674(85)90075-3. [DOI] [PubMed] [Google Scholar]
  15. Montesano R., Matsumoto K., Nakamura T., Orci L. Identification of a fibroblast-derived epithelial morphogen as hepatocyte growth factor. Cell. 1991 Nov 29;67(5):901–908. doi: 10.1016/0092-8674(91)90363-4. [DOI] [PubMed] [Google Scholar]
  16. Nakamura T. Structure and function of hepatocyte growth factor. Prog Growth Factor Res. 1991;3(1):67–85. doi: 10.1016/0955-2235(91)90014-u. [DOI] [PubMed] [Google Scholar]
  17. Park M., Dean M., Cooper C. S., Schmidt M., O'Brien S. J., Blair D. G., Vande Woude G. F. Mechanism of met oncogene activation. Cell. 1986 Jun 20;45(6):895–904. doi: 10.1016/0092-8674(86)90564-7. [DOI] [PubMed] [Google Scholar]
  18. Park M., Dean M., Kaul K., Braun M. J., Gonda M. A., Vande Woude G. Sequence of MET protooncogene cDNA has features characteristic of the tyrosine kinase family of growth-factor receptors. Proc Natl Acad Sci U S A. 1987 Sep;84(18):6379–6383. doi: 10.1073/pnas.84.18.6379. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Rodrigues G. A., Park M. Dimerization mediated through a leucine zipper activates the oncogenic potential of the met receptor tyrosine kinase. Mol Cell Biol. 1993 Nov;13(11):6711–6722. doi: 10.1128/mcb.13.11.6711. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Rong S., Jeffers M., Resau J. H., Tsarfaty I., Oskarsson M., Vande Woude G. F. Met expression and sarcoma tumorigenicity. Cancer Res. 1993 Nov 15;53(22):5355–5360. [PubMed] [Google Scholar]
  21. Rong S., Segal S., Anver M., Resau J. H., Vande Woude G. F. Invasiveness and metastasis of NIH 3T3 cells induced by Met-hepatocyte growth factor/scatter factor autocrine stimulation. Proc Natl Acad Sci U S A. 1994 May 24;91(11):4731–4735. doi: 10.1073/pnas.91.11.4731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Roussel M. F., Downing J. R., Rettenmier C. W., Sherr C. J. A point mutation in the extracellular domain of the human CSF-1 receptor (c-fms proto-oncogene product) activates its transforming potential. Cell. 1988 Dec 23;55(6):979–988. doi: 10.1016/0092-8674(88)90243-7. [DOI] [PubMed] [Google Scholar]
  23. Tsarfaty I., Resau J. H., Rulong S., Keydar I., Faletto D. L., Vande Woude G. F. The met proto-oncogene receptor and lumen formation. Science. 1992 Aug 28;257(5074):1258–1261. doi: 10.1126/science.1387731. [DOI] [PubMed] [Google Scholar]
  24. Wang T. C., Cardiff R. D., Zukerberg L., Lees E., Arnold A., Schmidt E. V. Mammary hyperplasia and carcinoma in MMTV-cyclin D1 transgenic mice. Nature. 1994 Jun 23;369(6482):669–671. doi: 10.1038/369669a0. [DOI] [PubMed] [Google Scholar]
  25. Weidner K. M., Behrens J., Vandekerckhove J., Birchmeier W. Scatter factor: molecular characteristics and effect on the invasiveness of epithelial cells. J Cell Biol. 1990 Nov;111(5 Pt 1):2097–2108. doi: 10.1083/jcb.111.5.2097. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Woolford J., McAuliffe A., Rohrschneider L. R. Activation of the feline c-fms proto-oncogene: multiple alterations are required to generate a fully transformed phenotype. Cell. 1988 Dec 23;55(6):965–977. doi: 10.1016/0092-8674(88)90242-5. [DOI] [PubMed] [Google Scholar]