Elsevier

Differentiation

Volume 38, Issue 1, June 1988, Pages 60-66
Differentiation

Human bronchial epithelial cells with integrated SV40 virus T antigen genes retain the ability to undergo squamous differentiation

https://doi.org/10.1111/j.1432-0436.1988.tb00592.xGet rights and content

Summary

Human bronchial epithelial cells transformed by either DNA virus infection (SV40 or Adenovirus 12-SV40 hybrid virus) or transfection with the SV40 large T antigen gene were studied for their ability to undergo squamous differentiation when exposed to 12-O-tetradecanoylphorbol-13 acetate (TPA), transforming growth factor-β1 (TGF-β1), or fetal bovine serum (FBS), agents that induce the squamous differentiation of normal human bronchial epithelial cells. Squamous differentiation occurred in all ten T-antigen-positive cell cultures when they were exposed to either FBS or TGF-β1, but none differentiated when exposed to TPA. From one cell line, designated BEAS-2B, two subclones were isolated, one of which was induced to undergo squamous differentiation by FBS, and a second that failed to undergo squamous differentiation and was mitogenically stimulated when exposed to serum. These phenotypically different subclones provide a new in vitro cellular system for delineating the mechanism(s) of human bronchial epithelial cell squamous differentiation in response to FBS or TGF-β1

References (49)

  • JJ Thompson et al.

    Barrett's metaplasia and adenocarcinoma of the esophagus and gastroesophageal junction

    Hum Pathol

    (1983)
  • P Zabos et al.

    Effect of L-ethionine on macromolecular synthesis in mitogen stimulated lymphocytes

    Biochim Biophys Acta

    (1978)
  • RK Assoian et al.

    Transforming growth factors in nonncoplastic tissues and their role in controlling cell growth

  • SP Banks-Schlegel et al.

    Differentiation of human epidermal cells transformed by SV40

    J Cell Biol

    (1983)
  • LA Barrett et al.

    Long-term organ culture of human bronchial epithelium

    Cancer Res

    (1976)
  • JY Chou

    Human placental cells transformed by tsA mutants of simian virus 40: A model system for the study of placental functions

    Proc Natl Acad Sci USA

    (1978)
  • JY Chou

    Establishment of clonal human placental cells synthesizing human choriogonadotropin

    Proc Natl Acad Sci USA

    (1978)
  • JJ Collins et al.

    Transformation by simian virus 40 of spleen cells from a hyper-immune rabbit: evidence for synthesis of immunoglobulin by the transformed cells

    Proc Natl Acad Sci USA

    (1974)
  • LJ Deftos et al.

    Parathyroid hormone production in vitro by human parathyroid cells transformed by simian virus 40

    Science

    (1968)
  • CC Harris

    Respiratory carcinogenesis and cancer epidemiology

  • CC Harris

    Human tissues and cells in carcinogenesis research

    Cancer Res

    (1987)
  • TW Hesterberg et al.

    Subpopulations of human bronchial epithelial cells in culture respond heterogeneously to 12-O-tetradecanoylphor-bol-12-acetate (TPA) and other modulations of differentiation

    Carcinogenesis

    (1987)
  • U Kikkawa et al.

    Protein kinase C as a possible receptor protein of tumor-promoting phorbol esters

    J Biol Chem

    (1986)
  • A Kraevskii

    Classification and pathological anatomy of lung cancer

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