title: Id1 gene expression is up-regulated in hyperplastic and neoplastic thyroid tissue and regulates growth and differentiation in thyroid cancer cells.
abstract: The Id (inhibitor of DNA binding) proteins are a family of helix-loop-helix (HLH) proteins (Id1, Id2, Id3, and Id4) that lack the basic domain necessary for DNA binding. The Id1 protein enhances cell proliferation and inhibits cellular differentiation in a variety of cell types. We have previously demonstrated that the Id1 gene is up-regulated in papillary and medullary thyroid cancers. In this study we characterized the expression and distribution of the Id1 protein in normal, hyperplastic, and neoplastic human thyroid tissue. We also evaluated the effect of the Id1 gene on thyroid cancer cell growth and markers of thyroid cell differentiation. We used semiquantitative immunohistochemistry to characterize Id1 protein expression in normal, hyperplastic (multinodular goiter and Graves' disease), and neoplastic thyroid tissue from 103 patients. Normal thyroid tissue had the lowest level of Id1 protein expression (P < 0.0001). Anaplastic thyroid cancer had the highest level (vs. benign and malignant thyroid tissues, P < 0.01). Id1 protein expression was higher in malignant thyroid tissue than in hyperplastic thyroid tissue (P < 0.02). We found no significant association between the level of Id1 protein expression and patient age, sex, tumor-node-metastasis stage, tumor size, primary tumor vs. lymph node metastasis, primary tumor vs. recurrent tumors, and extent of tumor differentiation. Inhibiting Id1 mRNA expression in thyroid cancer cell lines using Id1 antisense oligonucleotides resulted in growth inhibition (P < 0.03) and decreased thyroglobulin and sodium-iodine symporter mRNA expression (P < 0.02). In conclusion, Id1 is overexpressed in hyperplastic and neoplastic thyroid tissue and directly regulates the growth of thyroid cancer cells of follicular cell origin, but is not a marker of aggressive phenotype in differentiated thyroid cancer.
authors.affiliation: San Francisco Comprehensive Cancer Center, University of California, San Francisco, California 94143-1674, USA. kebebewe@surgery.ucsf.edu
authors.forename: Electron
authors.initials: E
authors.lastname: Kebebew
authors.forename: Miao
authors.initials: M
authors.lastname: Peng
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Treseler
authors.forename: Orlo H
authors.initials: OH
authors.lastname: Clark
authors.forename: Quan-Yang
authors.initials: QY
authors.lastname: Duh
authors.forename: David
authors.initials: D
authors.lastname: Ginzinger
authors.forename: Richard
authors.initials: R
authors.lastname: Miner
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D002455:Cell Division; D045744:Cell Line, Tumor; D005260:Female; D015870:Gene Expression; D006044:Goiter, Nodular / Q000378:metabolism* / Q000473:pathology*; D006111:Graves Disease / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D051798:Inhibitor of Differentiation Protein 1; D008297:Male; D008875:Middle Aged; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology*; D014018:Tissue Distribution; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1; D012097:Repressor Proteins; D014157:Transcription Factors