Differential expression of thyroperoxidase mRNA splice variants in human thyroid tumors.
The levels of human thyroperoxidase (hTPO) mRNA expression and the rates of hTPO mRNA with alternatively spliced exons 10, 14, and 16 were analyzed in normal, benign, and malignant thyroid tissues (13 normal thyroid tissues, 9 adenomas, 4 papillary carcinomas, 11 follicular variant of papillary carcinomas, 16 minimally invasive follicular carcinomas, 6 widely invasive follicular carcinomas) using a semi-quantitative reverse-transcription polymerase chain reaction procedure. The level of hTPO mRNA decreased in the follicular variant of papillary carcinomas and in minimally invasive follicular carcinomas and was more heterogeneous in the other pathological tissues than in normal tissues. Based on the mean values recorded, the splicing of exons 10 and 16 increased by at least 50% in all the carcinomas, as well as in the benign tissues in the case of exon 10. By contrast, no significant increase was observed in the splicing of exon 14 except in the case of the follicular variant of papillary carcinomas. In conclusion, the results of this study show that the splicing of hTPO increases in benign and malignant thyroid tissues. This event might partly explain the decrease in both the quantity and the level of activity of hTPO observed in thyroid cancer due to the loss of stability of the spliced isoforms. In addition, an increase in the alternative splicing of other mRNAs may contribute to the process of malignancy.
Le Fourn
Valérie
V
INSERM U555, Faculté de Médecine, 27 Bd J. Moulin, 13385 Marseille Cedex 5, France.
Ferrand
Mireille
M
Franc
Jean-Louis
JL
D000236:Adenoma / Q000201:enzymology / Q000235:genetics; D001324:Autoantigens / Q000235:genetics* / Q000378:metabolism*; D002291:Carcinoma, Papillary / Q000201:enzymology / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D005787:Gene Frequency; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation; D006801:Humans; D007453:Iodide Peroxidase / Q000235:genetics* / Q000378:metabolism*; D033862:Iron-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D022821:RNA Splice Sites / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D012016:Reference Values; D013964:Thyroid Neoplasms / Q000201:enzymology* / Q000235:genetics*
D001324:Autoantigens; D005819:Genetic Markers; D033862:Iron-Binding Proteins; D022821:RNA Splice Sites; D012333:RNA, Messenger; C056658:TPO protein, human; D007453:Iodide Peroxidase