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In vivo activation of STAT3 in cutaneous T-cell lymphoma. Evidence for an antiapoptotic function of STAT3

Leukemia volume 18, pages 1288–1295 (2004)Cite this article

Abstract

A characteristic feature of neoplastic transformation is a perpetual activation of oncogenic proteins. Here, we studied signal transducers and activators of transcription (STAT) in patients with mycosis fungoides (MF)/cutaneous T-cell lymphoma (CTCL). Malignant lymphocytes in dermal infiltrates of CTCL tumors showed frequent and intense nuclear staining with anti-PY-STAT3 antibody, indicating a constitutive activation of STAT3 in vivo in tumor stages. In contrast, only sporadic and faint staining was observed in indolent lesions of patch and plaque stages of MF. Moreover, neoplastic lymphocytes in the epidermal Pautrier abscesses associated with early stages of MF did not express activated STAT3. To address the role of STAT3 in survival/apoptosis, CTCL tumor cells from an advanced skin tumor were transfected with either wild-type STAT3 (STAT3wt) or dominant-negative STAT3 (STAT3D). Forced inducible expression of STAT3D triggered a significant increase in tumor cells undergoing apoptosis, whereas forced expression of STAT3wt or empty vector had no effect. In conclusion, a profound in vivo activation of STAT3 is observed in MF tumors but not in the early stages of MF. Moreover, STAT3 protects tumor cells from apoptosis in vitro. Taken together, these findings suggest that STAT3 is a malignancy factor in CTCL.

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Acknowledgements

This work was supported in part by the Danish Allergy Research Center, the Danish Research Councils, the Danish Biotechnological Center for Cellular Communication, the Novo Nordic Foundation, Fabrikant Vilhelm Pedersen og hustrus mindelegat, the Danish Medical Research Council (Det Sundhedsvidenskabelige Forskningsråd), the Danish Cancer Research Foundation (Dansk Kræftforsknings Fond), the Danish Cancer Society (Kræftens Bekæmpelse), the Alfred Benzon Foundation, the Dannins Foundation (Ingeborg og Leo Dannins Legat for Videnskabelig Forskning), The Johann Weiman f. Seedorff and Wife Foundation (Købmand i Odense Johann og Hanne Weimann f. Seedorff's Legat), the Carlsberg Foundation, the University of Copenhagen, PhD programme (for AW, CB, CGK, KWE), scholarship from The Danish Cancer Society (Kræftens Bekæmpelse) (for VHS), and the US National Cancer Institute.

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Author notes

  1. V H Sommer and O J Clemmensen: These two authors contributed equally to this work

Authors and Affiliations

  1. Institutes of Medical Microbiology and Immunology, University of Copenhagen, Copenhagen, Denmark

    V H Sommer, P Lovato, C Brender, K W Eriksen, A Woetmann, S Skov & N Ødum

  2. Department of Pathology, Odense University Hospital, Odense, Denmark

    O J Clemmensen & O Nielsen

  3. Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, PA, USA

    M Wasik

  4. Medical Anatomy, University of Copenhagen, Copenhagen, Denmark

    C G Kaestel, M H Nissen & C Ropke

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  1. V H Sommer
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Correspondence to N Ødum.

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Sommer, V., Clemmensen, O., Nielsen, O. et al. In vivo activation of STAT3 in cutaneous T-cell lymphoma. Evidence for an antiapoptotic function of STAT3. Leukemia 18, 1288–1295 (2004). https://doi.org/10.1038/sj.leu.2403385

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  • DOI: https://doi.org/10.1038/sj.leu.2403385

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