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Differentiation of pancreatic carcinoma induced by retinoic acid or sodium butyrate: a morphological and molecular analysis of four cell lines

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Abstract

The antiproliferative and differentiation-inducing effects of all-trans retinoic acid (RA) and sodium butyrate (SB) were investigated in four pancreatic ductal adenocarcinoma cell lines, two poorly differentiated ones (PT45 and PaTu-II), one moderately to poorly differentiated one (Panc-1) and one highly differentiated one (A818-1). Treatment with 20 μM RA resulted in moderate inhibition of cell growth in all cell lines, but clear evidence of cytodifferentiation (including elongated cell processes, increased rough endoplasmic reticulum, intensified immunostaining for the mucin marker M1) was found only in PT45 and Panc-1. These phenotypic changes were paralleled by upregulation of RAR (retinoic acid receptor)-α and -γ mRNA. SB (1 and 2 mM) treatment inhibited the cell growth of all cell lines much more prominently than RA. Cytodifferentiation was also largely restricted to PT45 and Panc-1. A noticeable phenomenon was enhancement of the expression of the neuroendocrine markers synaptophysin and Leu7 in Panc-1 cells. In conclusion, it is evident that the original differentiation status of cells and their responsiveness to the agents are not clearly associated, and that RA responsiveness correlates with upregulation of RAR-α and -γ mRNA.

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Authors and Affiliations

  1. Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, Japan

    Naoto Egawa

  2. Department of Pathology, Academic Hospital Jette, Free University of Brussels, Brussels, Belgium

    Bernard Maillet

  3. Departments of Medical Genetics, Medical Oncology and Hematology, Academic Hospital Jette, Free University of Brussels, Brussels, Belgium

    Brigitte VanDamme & Jacques De Grève

  4. Department of Pathology, University of Kiel, Michaelisstrasse 11, D-24105, Kiel, Germany

    Göunter Klöppel

Authors
  1. Naoto Egawa
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  2. Bernard Maillet
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  3. Brigitte VanDamme
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  4. Jacques De Grève
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  5. Göunter Klöppel
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Dedicated to Prof. G. Seifert on the occasion of his 75th birthday

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Egawa, N., Maillet, B., VanDamme, B. et al. Differentiation of pancreatic carcinoma induced by retinoic acid or sodium butyrate: a morphological and molecular analysis of four cell lines. Vichows Archiv A Pathol Anat 429, 59–68 (1996). https://doi.org/10.1007/BF00196822

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  • DOI: https://doi.org/10.1007/BF00196822

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