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Expression and Localization of the Homeodomain-Containing Protein HEX in Human Thyroid Tumors

Dipartimento di Scienze e Tecnologie Biomediche and Dipartimento di Scienze Mediche e Morfologiche (A.V.D., F.P., P.C., C.D., G.D.), Università di Udine, 33100 Udine, Italy; Microgravity Aging Training Immobility Center (A.V.D., G.D.), Udine, Italy; Dipartimento di Biofisica, Biochimica e Chimica delle Macromolecole (G.T., G.M.), Università di Trieste, I-34127 Trieste, Italy; Dipartimento di Scienze Farmacobiologiche and Dipartimento di Medicina Sperimentale e Clinica (D.R., F.A., S.F.), Università di Catanzaro, 88100 Catanzaro, Italy; Clinical and Experimental Hematology Research Unit (V.G.), Centro di Riferimento Oncologico, Instituto di Ricovero e Cura a Carattere Scientifico, 33081 Aviano, Italy; Indiana Cancer Research Institute (D.L.M.), Indianapolis, Indiana, IN 46202-5254

Address all correspondence and requests for reprints to: Prof. Giuseppe Damante, Dipartimento di Scienze e Tecnologie Biomediche, Piazzale Kolbe 1-33100 Udine, Italy. E-mail: . GDamante{at}makek.dstb.uniud.it

Abstract

Homeobox genes are involved in neoplastic transformation of both epithelial and hemopoietic tissues. The divergent homeobox gene HEX is expressed in the anterior visceral endoderm during early mouse development and in some adult tissues of endodermal origin, including liver and thyroid. Whereas a role in leukemyogenesis has been proposed already, few data are available on the involvement of HEX in human epithelial tumors. Herein, we analyzed HEX expression and subcellular localization in a series of 55 human thyroid tumors and in several tumoral cell lines. HEX mRNA was detected by RT-PCR either in normal tissues or in thyroid adenomas and differentiated (papillary and follicular) carcinomas. HEX mRNA was also expressed in most undifferentiated carcinomas. Subcellular localization of HEX protein was investigated by immunohistochemistry. In normal tissues and adenomas, HEX protein was present both in nucleus and cytoplasm. In contrast, both differentiated and undifferentiated carcinomas, as well as the tumoral cell lines investigated, showed HEX protein only in the cytoplasm. These findings suggest that regulation of HEX entry in the nucleus of thyrocytes may represent a critical step during human thyroid tumorigenesis.

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