Cloning of the rat tissue inhibitor of metalloproteinases type 2 (TIMP-2) gene: analysis of its expression in normal and transformed thyroid cells.
We have recently reported that the introduction of the E1A gene of the adenovirus 5 gene into the rat thyroid PC Cl 3 epithelial cell line causes loss of the differentiated thyroid phenotype without the appearance of the typical markers of neoplastic transformation. It is well known that the E1A gene is able either to induce or to repress the transcription of various endogenous cellular genes. In order to characterize the genes involved in the transformation of PC Cl 3 cells by the E1A gene, we have isolated several cDNA clones, whose expression was induced by E1A. One of these clones was found to be the rat homologue of the human tissue inhibitor of metalloproteinase type 2 (TIMP-2) gene. Here we show the complete sequence of the rat TIMP-2. Its homology to the human TIMP-2 is 98% at the amino acid level and, like its human counterpart, the rat TIMP-2 is transcribed in two different mRNAs of 1.0 and 3.5 kb. The expression of TIMP-2, in PC Cl 3 cells, was significantly induced by the E1A gene and also by other oncogenes. Finally TIMP-2 was shown to be significantly overexpressed in human thyroid neoplastic cell lines and some tumoral thyroid samples.
Santoro
M
M
Centro di Endocrinologia ed Oncologia Sperimentale del C.N.R., Facoltà di Medicina e Chirurgia, Università degli Studi di Napoli, Italy.
Battaglia
C
C
Zhang
L
L
Carlomagno
F
F
Martelli
M L
ML
Salvatore
D
D
Fusco
A
A
D017500:Adenovirus E1A Proteins / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004247:DNA; D005786:Gene Expression Regulation; D006801:Humans; D008969:Molecular Sequence Data; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017386:Sequence Homology, Amino Acid; D013961:Thyroid Gland / Q000166:cytology / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2
D017500:Adenovirus E1A Proteins; D011506:Proteins; D019716:Tissue Inhibitor of Metalloproteinase-2; D004247:DNA