The helix-loop-helix protein, Id-1, is overexpressed and regulates growth in papillary thyroid cancer.
BACKGROUND
Members of the Id helix-loop-helix proteins are key regulators of cell growth and differentiation in a variety of cell types. They are also required for cell cycle progression and regulate tumor angiogenesis. Furthermore, deregulated expression of Id proteins has been observed in some human malignancies. Therefore we hypothesized that the Id-1 gene may play a role in papillary thyroid carcinogenesis.


METHODS
Id-1 gene expression was characterized by Northern blot analysis and Id-1 immunohistochemistry in human thyroid tissue. Id-1 gene expression and regulation was evaluated in a human papillary thyroid cancer cell line, TPC-1, by Northern blot analysis.


RESULTS
The Id-1 gene was significantly overexpressed in papillary thyroid cancer compared with normal thyroid tissue from the same patients (n = 18) by both Northern blot analysis and semiquantitative Id-1 immunohistochemistry (P <.001). Id-1 immunoreactivity was primarily localized to the cytoplasm of the thyroid follicular cells. In the TPC-1 cell line, stimulation by TSH and serum up-regulated Id-1 mRNA expression 1.5- and 4.0-fold, respectively. Activation of the mitogen intracellular protein kinase A and protein kinase C signaling pathways also up-regulated Id-1 mRNA expression. Inhibition of Id-1 mRNA expression with Id-1 antisense oligonucleotide inhibited growth compared with control Id-1 sense and random oligonucleotides (P <.05).


CONCLUSIONS
The Id-1 gene is overexpressed in papillary thyroid cancer. Id-1 may play a role in the regulation of growth in papillary thyroid cancer.
Kebebew
Electron
E
Department of Surgery/Department of Pathology, University of California, San Francisco, CA 94143, USA.
Treseler
Patrick A
PA
Duh
Quan-Yang
QY
Clark
Orlo H
OH
D015152:Blotting, Northern; D002291:Carcinoma, Papillary / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D051798:Inhibitor of Differentiation Protein 1; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins; D013961:Thyroid Gland / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D014018:Tissue Distribution; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1; D012097:Repressor Proteins; D014157:Transcription Factors