Id1 Gene Expression Is Up-Regulated in Hyperplastic and Neoplastic Thyroid Tissue and Regulates Growth and Differentiation in Thyroid Cancer Cells (original) (raw)

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1San Francisco Comprehensive Cancer Center (E.K., P.A.T., O.H.C., D.G.), California 94143-1674

2Departments of Surgery (E.K., M.P., O.H.C., Q.-Y.D., R.M.), California 94143-1674

*Address all correspondence and requests for reprints to: Dr. Electron Kebebew, Department of Surgery, University of California/Mount Zion Medical Center, San Francisco, California 94143-1674.

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2Departments of Surgery (E.K., M.P., O.H.C., Q.-Y.D., R.M.), California 94143-1674

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1San Francisco Comprehensive Cancer Center (E.K., P.A.T., O.H.C., D.G.), California 94143-1674

3Pathology (P.A.T.), University of California, San Francisco, California 94143-1674

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1San Francisco Comprehensive Cancer Center (E.K., P.A.T., O.H.C., D.G.), California 94143-1674

2Departments of Surgery (E.K., M.P., O.H.C., Q.-Y.D., R.M.), California 94143-1674

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2Departments of Surgery (E.K., M.P., O.H.C., Q.-Y.D., R.M.), California 94143-1674

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1San Francisco Comprehensive Cancer Center (E.K., P.A.T., O.H.C., D.G.), California 94143-1674

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2Departments of Surgery (E.K., M.P., O.H.C., Q.-Y.D., R.M.), California 94143-1674

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Accepted:

09 September 2004

Published:

01 December 2004

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Electron Kebebew, Miao Peng, Patrick A. Treseler, Orlo H. Clark, Quan-Yang Duh, David Ginzinger, Richard Miner, Id1 Gene Expression Is Up-Regulated in Hyperplastic and Neoplastic Thyroid Tissue and Regulates Growth and Differentiation in Thyroid Cancer Cells, The Journal of Clinical Endocrinology & Metabolism, Volume 89, Issue 12, 1 December 2004, Pages 6105–6111, https://doi.org/10.1210/jc.2004-1234
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Abstract

The Id (_i_nhibitor of _D_NA 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.

Copyright © 2004 by The Endocrine Society

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