Thyroid cell transformation requires the expression of the HMGA1 proteins.
Elevated expression of HMGA1 and HMGA2 proteins is correlated with a highly malignant phenotype in several human tumors. We previously demonstrated that the block of HMGA2 protein synthesis prevented rat thyroid cell transformation by murine retroviruses. Suppression of HMGA2 synthesis was associated with lack of induction of HMGA1 proteins suggesting that both HMGA1 and HMGA2 play a role in the process of neoplastic transformation. To determine the role of the HMGA1 gene in thyroid cell transformation, we blocked HMGA1 protein synthesis by an antisense methodology. Here we report that transfection of an HMGA1 cDNA antisense construct into a normal rat thyroid cell line (FRTL-5 Cl2), followed by infection with Kirsten murine sarcoma virus (KiMSV), generated a transformed cell line that expresses high levels of the v-ras-Ki oncogene and that does not require thyroid-stimulating hormones for growth. However, this cell line does not show the malignant phenotype, i.e., it neither grows in soft agar nor induces tumors after injection in athymic mice. Moreover, the lack of the neoplastic phenotype in the virus-infected thyroid cells carrying the HMGA1 antisense construct correlates with the absence of induction of AP-1 transcriptional activity.
Berlingieri
Maria Teresa
MT
Centro di Endocrinologia ed Oncologia Sperimentale del Consiglio Nazionale delle Ricerche c/o Dipartimento di Patologia Cellulare e Molecolare, Facoltà di Medicina e Chirurgia, Università degli Studi di Napoli, Via Pansini 5, 80131 Naples, Italy.
Pierantoni
Giovanna M
GM
Giancotti
Vincenzo
V
Santoro
Massimo
M
Fusco
Alfredo
A
D000818:Animals; D002461:Cell Line, Transformed / Q000637:transplantation; D002472:Cell Transformation, Viral / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D016373:DNA, Antisense / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D011905:Genes, ras; D025741:HMGA1a Protein / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D025743:HMGA2 Protein / Q000502:physiology; D007708:Kirsten murine sarcoma virus / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008819:Mice, Nude; D015689:Oncogene Protein p21(ras) / Q000502:physiology*; D010641:Phenotype; D051381:Rats; D011916:Rats, Inbred F344; D011993:Recombinant Fusion Proteins / Q000502:physiology; D013045:Species Specificity; D013961:Thyroid Gland / Q000166:cytology*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014162:Transfection; D014410:Tumor Stem Cell Assay
D016373:DNA, Antisense; D018076:DNA, Complementary; D025743:HMGA2 Protein; D011993:Recombinant Fusion Proteins; D018808:Transcription Factor AP-1; D025741:HMGA1a Protein; D015689:Oncogene Protein p21(ras)