Inhibited transformation of immortalized human bronchial epithelial cells by retinoic acid is linked to cyclin E down-regulation Journal Article

  


Authors: Langenfeld, J.; Lonardo, F.; Kiyokawa, H.; Passalaris, T.; Ahn, M. J.; Rusch, V.; Dmitrovsky, E.
Article Title: Inhibited transformation of immortalized human bronchial epithelial cells by retinoic acid is linked to cyclin E down-regulation
Abstract: The retinoids are reported to reduce second primary aerodigestive tract tumors in patients with prior lung or head and neck carcinomas. Yet, the optimal retinoid useful for chemoprevention and those mechanisms linked to this chemoprevention are not identified. This study reports an in vitro model for carcinogen-induced transformation of immortalized human bronchial epithelial (BEAS-2B) cells that was adapted to study the anticarcinogenic effects of all-trans-retinoic acid (RA). Following exposure to carcinogens: cigarette smoke condensate (CSC) or N-nitrosamine-4-(methylnitrosamino)-1-(3 pyridyl)-1-butanone (NNK), BEAS-2B cells exhibited evidence of transformation. This included an increased anchorage independent growth or acquired ability to form tumors in athymic mice. This transformation was inhibited by RA as demonstrated by a lack of augmented anchorage independent growth or tumor formation in athymic mice for the cells treated with RA. The BEAS-ZB cells transformed by NNK exhibited an increase in cyclin E expression which was associated with an increase in the cyclin E-Cdk2 kinase activity. Over-expression of human cyclin E by transfection shows cyclin E enhances the basal clonal growth of BEAS-2B cells. In both the parental and transformed BEAS-2B cells, RA down-regulated cyclin E protein levels which was associated with an inhibition of growth and an accumulation of cells in G1. The data reported here suggest the decline of cyclin E expression represents a potential mechanism for the RA-induced growth suppression which is linked to the anti-carcinogenic effects of RA. Thus, this study reports the adaption of an in vitro model of lung carcinogenesis suitable to test the activity of chemoprevention agents.
Keywords: controlled study; human cell; nonhuman; mouse; animals; mice; cells, cultured; cell cycle; cell division; models, biological; animal experiment; down-regulation; antineoplastic activity; enzyme activation; transfection; animalia; mus musculus; cell transformation, neoplastic; nude mouse; cell transformation; protein-serine-threonine kinases; carcinogenicity; simian virus 40; protein induction; epithelial cells; bronchus; cycline; bronchus mucosa; cyclin-dependent kinases; cyclins; cyclin dependent kinase; retinoic acid; anchorage independent growth; bronchi; cyclin e; adenoviridae; transformation; growth inhibition; carcinogen; cyclin-dependent kinase 2; rabbits; cell immortalization; drug evaluation; tretinoin; smoke; cigarette smoke condensate; nitrosamines; cdc2-cdc28 kinases; dna transfection; humans; human; priority journal; article; nitrosamine; bronchial epithelial cells
Journal Title: Oncogene
Volume: 13
Issue: 9
ISSN: 0950-9232
Publisher: Nature Publishing Group  
Date Published: 1996-11-07
Start Page: 1983
End Page: 1990
Language: English
PUBMED: 8934545
PROVIDER: scopus
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-0029956857&partnerID=40&md5=7bb5de08fffe981fa5554fea70bc51a1
Notes: Article -- Export Date: 22 November 2017 -- Source: Scopus
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MSK Authors
  1. Valerie W Rusch
    864 Rusch
  2. Fulvio B Lonardo
    23 Lonardo
  3. Ethan Dmitrovsky
    98 Dmitrovsky
  4. Hiroaki Kiyokawa
    27 Kiyokawa
  5. John E. Langenfeld
    14 Langenfeld
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