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Smad2 suppresses the growth of Mv1Lu cells subcutaneously inoculated in mice
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research.
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2004 (English)In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 40, no 2, 267-274 p.Article in journal (Refereed) Published
Abstract [en]

Smad2 and Smad3 are intracellular signal transduction proteins of importance in transforming growth factor-beta (TGFbeta)-mediated inhibition of epithelial cell proliferation. Inactivating mutations in the Smad2 and Smad3 genes have been found in various human malignancies. Here, we show that expression of Smad2 leads to the inhibition of growth of Mv1Lu cells inoculated with Matrigel subcutaneously (s.c.) in severe combined immunodeficient (SCID) mice. In histological appearance, the Matrigel plugs with Smad2-transfected cells showed strongly reduced cell density, proliferation and angiogenesis compared with the small tumour nodules of similar size formed by the vector- or Smad3-transfected cells. The histological appearance of vector- and Smad3-transfected cells inoculated in mice was identical. Overexpression of Smad2 and Smad3 in Mv1Lu cells led to the inhibition of cell growth in three-dimensional cultures when compared with vector-transfected cells. Overexpression of Smad2 and Smad3 also decreased the hyperphosphorylation of pRb in Smad-transfected cells. Thus, increased expression of Smad2 leads to inhibition of Mv1Lu cell proliferation and a reduction in the growth of the Smad2-expressing cells inoculated in mice.

Place, publisher, year, edition, pages
2004. Vol. 40, no 2, 267-274 p.
Keyword [en]
Animals, Blotting; Western, DNA-Binding Proteins/*genetics, Gene Expression, Genes; myc/genetics, Immunohistochemistry, Keratinocytes, Lung Neoplasms/*pathology, Mice, Mice; SCID, Neoplasm Transplantation, Phosphorylation, Proteins/genetics, Research Support; Non-U.S. Gov't, Trans-Activators/*genetics, Transfection, Tumor Cells; Cultured
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Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-72958DOI: 10.1016/j.ejca.2003.08.016PubMedID: 14728942OAI: oai:DiVA.org:uu-72958DiVA: diva2:100869
Available from: 2005-05-31 Created: 2005-05-31 Last updated: 2013-11-07Bibliographically approved

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Sjöblom, TobiasYakymovych, IhorHeldin, Carl-HenrikSouchelnytskyi, Serhiy

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