The helix-loop-helix transcription factor, Id-1, is overexpressed in medullary thyroid cancer.
BACKGROUND
The Id-1 helix-loop-helix protein inhibits differentiation and enhances cell proliferation. It is required for cell cycle progression. The Id-1 gene is highly expressed in a variety of tumor-derived cell lines. It increases after mitogen stimulation and is overexpressed in some human neoplasms. Therefore, we hypothesized that the Id-1 gene may play a role in medullary thyroid carcinogenesis.


METHODS
The expression of the Id-1 protein in human medullary thyroid cancer (MTC) and the corresponding normal thyroid tissue was determined by Id-1 immunohistochemistry. In a human MTC cell line (TT), the effects of growth stimulation and redifferentiation on Id-1 expression were determined by Northern blot analysis.


RESULTS
Id-1 immunostaining intensity in 9 MTC samples (6 sporadic, 2 familial, and 1 MEN 2A) was moderate to strong. However, it was absent or faint in the corresponding normal thyroid tissue. The Id-1 protein was significantly overexpressed in MTC compared with corresponding normal thyroid tissue on the basis of the percentage of positive cells and immunostaining intensity (P =.002). In the TT cell line, Id-1 messenger RNA (mRNA) expression was increased 4-fold after growth stimulation with serum. Phorbol ester (which induces redifferentiation in the TT cell line) downregulated Id-1 mRNA expression.


CONCLUSIONS
Id-1 is overexpressed in MTC. The Id-1 gene may play a role in the regulation of MTC differentiation and proliferation.
Kebebew
E
E
Department of Surgery, University of California, San Francisco, 91434-0470, USA.
Treseler
P A
PA
Duh
Q Y
QY
Clark
O H
OH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018276:Carcinoma, Medullary / Q000737:chemistry* / Q000473:pathology; D002648:Child; D004268:DNA-Binding Proteins / Q000032:analysis* / Q000235:genetics / Q000502:physiology; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D007150:Immunohistochemistry; D051798:Inhibitor of Differentiation Protein 1; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D012097:Repressor Proteins; D013964:Thyroid Neoplasms / Q000737:chemistry* / Q000473:pathology; D014157:Transcription Factors / Q000032:analysis* / Q000235:genetics / Q000502:physiology; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1; D012333:RNA, Messenger; D012097:Repressor Proteins; D014157:Transcription Factors