H-RAS gene expression in human multinodular goiter.
The RAS protooncogene has an important, although not yet established role in thyroid neoplasia. In this study, we evaluated the H-RAS mRNA and protein levels in human samples of nontoxic and toxic multinodular goiter samples, according to serum TSH levels. The mean of H-RAS mRNA levels in nodules of nontoxic nodular goiter were significantly increased compared to nonnodular tissue (1.49+/-1.21 vs. 0.94+/-0.81 AU, P=0.016). Nine of the 18 specimens (50%) of nontoxic multinodular goiter exhibited increased levels of H-RAS mRNA. The increased H-RAS mRNA levels were paralleled by inRAcreased H-Ras protein levels in about 90% of the cases. Interestingly, no differences were observed in H-RAS expression between nodules and adjacent nonnodular tissue in toxic nodular goiters (0.58+/-0.27 vs. 0.58+/-0.20 AU, P=0.88). None of the 10 samples from toxic multinodular goiters exhibited overexpression of H-RAS. The H-RAS expression was positively correlated with thyroglobulin expression (r2=0.51; P=0.04). In conclusion, we demonstrated increased levels of H-RAS mRNA and protein in samples of nontoxic multinodular goiter, indicating that it might be involved in goiter pathogenesis. In contrast, H-RAS overexpression was not detected in any of the samples of toxic multinodular goiter, suggesting different mechanisms for cell proliferation in nodular goiter according to thyroid status.
Golbert
L
L
Endocrine Division, Hospital de Clínicas de Porto Alegre, Federal University of Rio Grande do Sul, Brazil.
Kolling
J H G
JH
Leitão
A H
AH
Martins
L
L
Kimura
E T
ET
Maia
A L
AL
D000328:Adult; D000368:Aged; D049109:Cell Proliferation; D004252:DNA Mutational Analysis; D005260:Female; D015870:Gene Expression; D011905:Genes, ras; D006044:Goiter, Nodular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D015689:Oncogene Protein p21(ras) / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013954:Thyroglobulin / Q000378:metabolism; D013971:Thyrotoxicosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D013972:Thyrotropin / Q000378:metabolism
D012333:RNA, Messenger; D013972:Thyrotropin; D013954:Thyroglobulin; D015689:Oncogene Protein p21(ras)