Affiliation:
1. Centro di Endocrinologia ed Oncologia Sperimentale, Consiglio Nazionale delle Ricerche, Facoltà di Medicina e Chirurgia, Università degli Studi di Napoli, Italy.
Abstract
Elevated expression of the three high-mobility group I (HMGI) proteins (HMGI, HMGY, and HMGI-C) has previously been correlated with the presence of a highly malignant phenotype in epithelial and fibroblastic rat thyroid cells and in experimental thyroid, lung, mammary, and skin carcinomas. Northern (RNA) blot and run-on analyses demonstrated that the induction of HMGI genes in transformed thyroid cells occurs at the transcriptional level. An antisense methodology to block HMGI-C protein synthesis was then used to analyze the role of this protein in the process of thyroid cell transformation. Transfection of an antisense construct for the HMGI-C cDNA into normal thyroid cells, followed by infection with transforming myeloproliferative sarcoma virus or Kirsten murine sarcoma virus, generated cell lines that expressed significant levels of the retroviral transforming oncogenes v-mos or v-ras-Ki and removed the dependency on thyroid-stimulating hormones. However, in contrast with untransfected cells or cells transfected with the sense construct, those containing the antisense construct did not demonstrate the appearance of any malignant phenotypic markers (growth in soft agar and tumorigenicity in athymic mice). A great reduction of the HMGI-C protein levels and the absence of the HMGI(Y) proteins was observed in the HMGI-C antisense-transfected, virally infected cells. Therefore, the HMGI-C protein seems to play a key role in the transformation of these thyroid cells.
Publisher
American Society for Microbiology
Subject
Cell Biology,Molecular Biology
Reference47 articles.
1. Culture of hormone-dependent functional epithelial cells from rat thyroids;Ambesi-Impiombato F. S.;Proc. Natl. Acad. Sci. USA,1980
2. The role of Jun, Fos and AP-1 complex in cell proliferation and transformation;Angel P.;Biochim. Biophys. Acta,1991
3. Thyrotropin receptor gene expression in oncogene-transfected rat thyroid cells: correlation between transformation, loss of thyrotropin-dependent growth and loss of thyrotropine receptor gene expression;Berlingieri M. T.;Biochem. Biophys. Res. Commun.,1990
4. The block of thyroglobulin synthesis following transformation of rat thyroid cells is at transcriptional level and it is associated with methylation of the 5~ flanking region of the gene;Berlingieri M. T.;Exp. Cell Res.,1989
5. Cooperation between polyomavirus middle T gene and the human c-myc oncogene on a rat thyroid epithelial differentiated cell line: a model of in vitro progression;Berlingieri M. T.;Mol. Cell. Biol.,1988
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