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SEL1L expression in pancreatic adenocarcinoma parallels SMAD4 expression and delays tumor growth in vitro and in vivo

Oncogene volume 22, pages 6359–6368 (2003)Cite this article

Abstract

Recent data suggest that SEL1L may play an important role in pancreatic carcinoma, similar to breast cancer, where the expression of SEL1L has been associated with a reduction in both proliferative activity in vitro and clinical tumor aggressiveness. To investigate this possibility, we examined the expression of Sel1L in a series of primary pancreatic carcinomas by immunohistochemistry and characterized the effects of Sel1L overexpression both in vitro and in vivo. In 74 pancreatic cancers analysed, 36% lacked Sel1L expression, although there was no significant correlation between the expression of Sel1L and any clinicopathologic parameter, including survival. However, immunohistochemical reactivity for Sel1L and Dpc4/Smad4 was concordant in 69% of cases (χ2 test P<0.004). Overexpression of SEL1L in stably transfected pancreatic cancer cells caused both a decrease in clonogenicity and anchorage-independent growth as well as a significant increase in the levels of activin A and SMAD4. When implanted in nude mice, Suit-2-SEL1L-overexpressing clones displayed a considerably reduced rate of tumor growth. Thus, it can be hypothesized that Sel1L plays an important function in the growth and aggressiveness of pancreatic carcinoma. Moreover, our data provide evidence that SEL1L has an impact on the expression of genes involved in regulation of cellular growth, possibly through the TGF-β signaling pathway.

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Abbreviations

Mab:

monoclonal antibody

DEX:

dexamethasone

RT–PCR:

reverse transcription–PCR

HPRT:

hypoxanthine phosphoribosyltransferase

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Acknowledgements

This work was supported by grants from Associazione Italiana Ricerca Cancro, Milan, Italy to AS; Ministero Università (Cofin 2002068231 and 2001068593), Rome, Italy; European Community Grant QLG1-CT-2002-01196. MC is supported by a fellowship from Fondazione Italiana Ricerca sul Cancro (FIRC). PSM is supported by Fondazione Cassa di Risparmio di Verona (Bando 2001), Verona, Italy.

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Author notes

  1. Contributed equally to this work

Authors and Affiliations

  1. Institute for Biomedical Technologies (National Research Council), Milano, Italy

    Monica Cattaneo & Ida Biunno

  2. Department of Pathology, Università di Verona, Italy

    Simonetta Orlandini, Stefania Beghelli, Patrick S Moore, Claudio Sorio, Antonio Bonora, Giuseppe Zamboni & Aldo Scarpa

  3. Department of Surgical and Gastroenterological Sciences, Università di Verona, Italy

    Claudio Bassi & Giorgio Talamini

  4. Department of Experimental Oncology, Molecular Targeting Unit, Istituto Nazionale Tumori, Milan, Italy

    Rosaria Orlandi & Sylvie Ménard

  5. Centre of Excellence, University of Milan, Italy

    Luigi Rossi Bernardi

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  1. Monica Cattaneo
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Correspondence to Ida Biunno or Aldo Scarpa.

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Cattaneo, M., Orlandini, S., Beghelli, S. et al. SEL1L expression in pancreatic adenocarcinoma parallels SMAD4 expression and delays tumor growth in vitro and in vivo. Oncogene 22, 6359–6368 (2003). https://doi.org/10.1038/sj.onc.1206665

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