Gastroenterology

Gastroenterology

Volume 109, Issue 5, November 1995, Pages 1646-1660
Gastroenterology

Retinoids: Effects on growth, differentiation, and nuclear receptor expression in human pancreatic carcinoma cell lines,☆☆

https://doi.org/10.1016/0016-5085(95)90655-XGet rights and content

Abstract

Background & Aims Advanced pancreatic carcinoma has a dismal prognosis despite extensive chemotherapeutic trials. The aim of this study was to evaluate the role of retinoids as an experimental therapeutic approach for pancreatic cancer. Methods Four ductal and one acinar pancreatic tumor cell lines were investigated. Growth was determined by cell number and a human tumor clonogenic assay. In vivo growth was assessed by xenografts transplanted into nude mice. Differentiation was characterized by immunofluorescence microscopy and carbonic anhydrase II gene expression. Retinoid receptors were characterized by Northern blotting and reverse-transcriptase polymerase chain reaction. Results Retinoid treatment results in a time- and dose-dependent growth inhibition in vitro and in vivo of ductal but not acinar pancreatic tumor cells. Retinoid treatment induces a more differentiated phenotype in ductal tumor cells as shown by morphological criteria and increased expression of carbonic anhydrase II. All pancreatic tumor cell lines expressed a broad panel of cellular retinoid binding proteins and nuclear retinoid receptors. Retinoic acid receptor γ and cellular retinoic acid binding protein II were found in all retinoid-sensitive ductal tumor cell lines but not in the retinoid-resistant acinar cell lines. Conclusions Detailed knowledge of nuclear retinoid receptor expression may provide rational strategies for retinoid treatment of pancreatic cancer.

References (38)

  • W Bollag et al.

    Retinoids in cancer prevention and therapy

    Ann Oncol

    (1992)
  • V Giguere

    Retinoic acid receptors and cellular retinoid binding proteins: complex interplay in retinoid signaling

    Endocr Rev

    (1994)
  • B Houle et al.

    Tumor-suppressive effect of the retinoic acid receptor β in human epidermoid lung cell cancer cells

  • H de The et al.

    The t(17:15) translocation of acute promyelocytic leukemia fuses the retinoic acid receptor α gene to a novel transcribed locus

    Nature

    (1990)
  • S Rosewicz et al.

    An amphicrine pancreatic cell line: AR42J cells combine exocrine and neuroendocrine properties

    Eur J Cell Biol

    (1992)
  • JM Chirgwin et al.

    Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease

    Biochemistry

    (1979)
  • S Rosewicz et al.

    Bombesin receptor gene transcription in rat pancreatic acinar AR42J cells: transcriptional regulation by glucocorticoids

    Gastroenterology

    (1994)
  • M Petkovich et al.

    A human retinoic acid receptor which belongs to the family of nuclear receptors

    Nature

    (1987)
  • N Brand et al.

    Identification of a second human retinoic acid receptor

    Nature

    (1988)
  • Cited by (0)

    Supported by grant W50/93/Ro1 from the Deutsche Krebshilfe and by the Maria Sonnenfeld Gedächtnisstiftung.

    ☆☆

    The authors thank Drs. P. Chambon, P. Venta, and R. Evans for providing us with the complementary DNA probes.

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