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HMGA1 protein expression sensitizes cells to cisplatin-induced cell death

Oncogene volume 24, pages 6809–6819 (2005)Cite this article

Abstract

HMGA1 proteins belong to a family of nonhistone chromatin proteins able to bind DNA in AT-rich regions and to interact with various transcription factors thus enhancing or inhibiting gene transcription by acting as architectural proteins. Although their expression is very low or absent in many adult tissues, HMGA1 proteins have been frequently found to be upregulated in human cancers and are expressed at high levels during embryogenesis, suggesting they could have a role in highly proliferating cells. We have previously demonstrated that HMGA1 expression in primary breast cancer and mammary carcinoma derived cell lines inversely correlated with BRCA1 expression and that HMGA1 is able to downregulate the expression of BRCA1 gene by binding directly to its promoter region. Being BRCA1 protein expression strictly linked to the DNA repair activity of the cell, we investigated whether HMGA1 expression was able to influence cellular responses to DNA damage. Here, we report that high expression levels of HMGA1 proteins in MCF-7 or mouse embryonic stem cells results in diminished BRCA1 expression and enhanced sensitivity to Cisplatin and Bleomycin. The increased DNA damage-induced cell death in HMGA1-expressing cells is likely due to a diminished cellular DNA repair activity. Therefore, we propose that high expression of HMGA1 protein in human malignant neoplasias, acting on BRCA1 expression, could contribute to the progression of malignant transformation influencing the response of the cells to the damaged DNA.

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Acknowledgements

B Belletti is supported by an EMBO restart fellowship. Supported by Grants P01CA76259 and P30CA56036 from the National Cancer Institute to CM Croce and by grants from the Associazione Italiana Ricerca sul Cancro (AIRC) to A Fusco and G Baldassarre.

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Authors and Affiliations

  1. Kimmel Cancer Center, Jefferson Medical College, Philadelphia, 19107, PA, USA

    Gustavo Baldassarre, Barbara Belletti, Sabrina Battista, Francesca Pentimalli & Carlo M Croce

  2. Divisione di Oncologia Sperimentale 2, Centro di Riferimento Oncologico, Aviano, 33081, Italy

    Gustavo Baldassarre, Barbara Belletti & Milena S Nicoloso

  3. Dipartimento di Biologia e Patologia Cellulare e Molecolare c/o Centro di Endocrinologia ed Oncologia Sperimentale del CNR, Facoltà di Medicina e Chirurgia, Università degli Studi di Napoli ‘Federico II’, Via Pansini 5, Naples, 80131, Italy

    Sabrina Battista, Francesca Pentimalli, Monica Fedele & Alfredo Fusco

  4. Division of Human Cancer Genetics,Comprehensive Cancer Center, The Ohio State University, 10 West 12th Avenue, Columbus, 43210, OH, USA

    Carlo M Croce

  5. NOGEC (Naples Oncogenomic Center)-CEINGE, Centro di Biotecnologie Avanzate, via Comunale Margherita 482, Naples, 80145-, Italy

    Alfredo Fusco

Authors
  1. Gustavo Baldassarre
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  2. Barbara Belletti
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  3. Sabrina Battista
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  4. Milena S Nicoloso
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  6. Monica Fedele
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  7. Carlo M Croce
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  8. Alfredo Fusco
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Correspondence to Alfredo Fusco.

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Baldassarre, G., Belletti, B., Battista, S. et al. HMGA1 protein expression sensitizes cells to cisplatin-induced cell death. Oncogene 24, 6809–6819 (2005). https://doi.org/10.1038/sj.onc.1208831

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