The helix-loop-helix transcription factor, Id-1, is overexpressed in medullary thyroid cancer

Abstract

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.