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Expression of thyroid hormone receptor/erbA genes is altered in human breast cancer

Oncogene volume 21, pages 4307–4316 (2002)Cite this article

Abstract

The relation between thyroid status and diseases and cancer is unclear. No detailed analysis of thyroid hormone receptor (TR) expression in human breast cancer has been reported. We have analysed the expression and mutational status of the TRα1, encoded by the c-erbA proto-oncogene, TRβ1 and TRβ2 isoforms in 70 sporadic breast cancers. Alterations in the RNA level of TRβ1, TRα1, or both were found in a number of patients. No expression of TRβ2 RNA was detected. Western blotting analysis confirmed the differences in expression at the protein level in those cases where sufficient tumor sample was available. Additionally, tumor-specific truncated TRβ1 RNA was found in six patients. Strikingly, three transcripts shared the same breakpoint. Only one tumor carried the corresponding deletion at the genomic DNA level, suggesting that the remaining abnormal TRβ1 transcripts are aberrant splicing products. Though no significant correlation was found between TRβ1 alteration and any clinical parameter, it showed a tendency to associate with early age of onset (<50 years). Our results reveal specific alterations in the expression of TRβ and TRα genes in a subset of breast cancer patients, suggesting that deregulation of thyroid hormone target genes may be involved in the generation of this neoplasia.

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Acknowledgements

We thank Dr Leslie DeGroot from the University of Chicago for providing us with the anti-TR antibodies, Drs Manuel Serrano and Angel Zaballos from Centro Nacional de Biotecnología, Madrid for their help with the real-time PCR and use of LightCycler facilities, Dr Ana Cuadrado for her help with the Western blot assays, and Robin Rycroft for English language revision. This work was supported by Grants 08.1/0042/1998 and 08.1/0069/20002 from Comunidad Autónoma de Madrid, Spain.

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Authors and Affiliations

  1. Department of Medical Oncology, Clínica Puerta de Hierro, Madrid, E-28035, Spain

    José M Silva, Gemma Domínguez, José M García, Javier Silva & Félix Bonilla

  2. Department of Pathology, Hospital Santa Cristina, Madrid, E-28009, Spain

    Carmen García-Andrade

  3. Department of Pathology, Clínica Puerta de Hierro, Madrid, E-28035, Spain

    Antonia Navarro

  4. Instituto de Investigaciones Biomédicas ‘Alberto Sols’, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Madrid, E-28029, Spain

    José M González-Sancho & Alberto Muñoz

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  1. José M Silva
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Correspondence to Félix Bonilla.

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Silva, J., Domínguez, G., González-Sancho, J. et al. Expression of thyroid hormone receptor/erbA genes is altered in human breast cancer. Oncogene 21, 4307–4316 (2002). https://doi.org/10.1038/sj.onc.1205534

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