Open Access Research article

HEX expression and localization in normal mammary gland and breast carcinoma

Cinzia Puppin1, Fabio Puglisi25, Lucia Pellizzari3, Guidalberto Manfioletti4, Marta Pestrin2, Maura Pandolfi2, Andrea Piga2, Carla Di Loreto25 and Giuseppe Damante15*

Author Affiliations

1 Dipartimento di Scienze e Tecnologie Biomediche, Università di Udine, Italy

2 Dipartimento di Scienze Mediche e Morfologiche, Università di Udine, Italy

3 Istituto di Genetica del Policlinico Universitario, Università di Udine, Italy

4 Dipartimento di Biofisica, Biochimica e Chimica delle Macromolecole, Università di Trieste, Italy

5 Associazione Ricerca Traslazionale In Senologia

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BMC Cancer 2006, 6:192  doi:10.1186/1471-2407-6-192

Published: 19 July 2006

Abstract

Background

The homeobox gene HEX is expressed in several cell types during different phases of animal development. It encodes for a protein localized in both the nucleus and the cytoplasm. During early mouse development, HEX is expressed in the primitive endoderm of blastocyst. Later, HEX is expressed in developing thyroid, liver, lung, as well as in haematopoietic progenitors and endothelial cells. Absence of nuclear expression has been observed during neoplastic transformation of the thyroid follicular cells. Aim of the present study was to evaluate the localization and the function of the protein HEX in normal and tumoral breast tissues and in breast cancer cell lines.

Methods

HEX expression and nuclear localization were investigated by immunohistochemistry in normal and cancerous breast tissue, as well as in breast cancer cell lines. HEX mRNA levels were evaluated by real-time PCR. Effects of HEX expression on Sodium Iodide Symporter (NIS) gene promoter activity was investigated by HeLa cell transfection.

Results

In normal breast HEX was detected both in the nucleus and in the cytoplasm. In both ductal and lobular breast carcinomas, a great reduction of nuclear HEX was observed. In several cells from normal breast tissue as well as in MCF-7 and T47D cell line, HEX was observed in the nucleolus. MCF-7 treatment with all-trans retinoic acid enhanced HEX expression and induced a diffuse nuclear localization. Enhanced HEX expression and diffuse nuclear localization were also obtained when MCF-7 cells were treated with inhibitors of histone deacetylases such as sodium butyrate and trichostatin A. With respect to normal non-lactating breast, the amount of nuclear HEX was greatly increased in lactating tissue. Transfection experiments demonstrated that HEX is able to up-regulate the activity of NIS promoter.

Conclusion

Our data indicate that localization of HEX is regulated in epithelial breast cells. Since modification of localization occurs during lactation and tumorigenesis, we suggest that HEX may play a role in differentiation of the epithelial breast cell.