Down-regulation and antiproliferative role of C/EBPα in lung cancer

Balazs Halmos, Claudia S. Huettner, Olivier Kocher, Katalin Ferenczi, Daniel D. Karp, Daniel G. Tenen

Research output: Contribution to journalArticle

107 Citations (Scopus)

Abstract

The transcription factor, CCAAT/enhancer binding protein α (C/EBPα) is important in the terminal differentiation of granulocytes, hepatocytes, and adipocytes, and recurrent mutations of C/EBPα were described in acute myeloid leukemia. In the lung, C/EBPα is expressed in bronchial cells and type II pneumocytes. Abnormal proliferation of the latter cell type was reported in C/EBPα knockout mice. We determined the expression of C/EBPα by Northern blot analysis in 30 lung cancer cell lines and found significant down-regulation in 24 cell lines. Immunohistochemical study of primary tumor specimens showed undetectable or low expression of C/EBPα in 23 of 53 specimens. Its expression was more frequently down-regulated in adenocarcinoma and poorly differentiated cancer specimens than in squamous cell cancers. A higher frequency of reduced expression was found in more advanced stages. To investigate the consequences of C/EBPα expression in lung cancer cells, we stably transfected two cell lines that do not express the gene (Calu1 and H358) with a plasmid allowing for induction of C/EBPα protein expression. Induction of C/EBPα led to significant growth reduction attributable to proliferation arrest, morphological changes characteristic of differentiation, and apoptosis. These results suggest that C/EBPα is down-regulated in a large proportion of lung cancers and that it has growth-inhibitory properties in airway epithelial cells. Genetic analysis of the C/EBPα gene is in progress to fully evaluate its role as a novel tumor suppressor in lung cancer.

Original languageEnglish (US)
Pages (from-to)528-534
Number of pages7
JournalCancer Research
Volume62
Issue number2
StatePublished - Jan 15 2002
Externally publishedYes

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CCAAT-Enhancer-Binding Proteins
Lung Neoplasms
Down-Regulation
Cell Line
Alveolar Epithelial Cells
Squamous Cell Neoplasms
Neoplasms
Growth
Granulocytes
Adipocytes
Acute Myeloid Leukemia
Knockout Mice
Northern Blotting
Genes
Hepatocytes
Adenocarcinoma
Plasmids
Transcription Factors

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Halmos, B., Huettner, C. S., Kocher, O., Ferenczi, K., Karp, D. D., & Tenen, D. G. (2002). Down-regulation and antiproliferative role of C/EBPα in lung cancer. Cancer Research, 62(2), 528-534.

Down-regulation and antiproliferative role of C/EBPα in lung cancer. / Halmos, Balazs; Huettner, Claudia S.; Kocher, Olivier; Ferenczi, Katalin; Karp, Daniel D.; Tenen, Daniel G.

In: Cancer Research, Vol. 62, No. 2, 15.01.2002, p. 528-534.

Research output: Contribution to journalArticle

Halmos, B, Huettner, CS, Kocher, O, Ferenczi, K, Karp, DD & Tenen, DG 2002, 'Down-regulation and antiproliferative role of C/EBPα in lung cancer', Cancer Research, vol. 62, no. 2, pp. 528-534.
Halmos B, Huettner CS, Kocher O, Ferenczi K, Karp DD, Tenen DG. Down-regulation and antiproliferative role of C/EBPα in lung cancer. Cancer Research. 2002 Jan 15;62(2):528-534.
Halmos, Balazs ; Huettner, Claudia S. ; Kocher, Olivier ; Ferenczi, Katalin ; Karp, Daniel D. ; Tenen, Daniel G. / Down-regulation and antiproliferative role of C/EBPα in lung cancer. In: Cancer Research. 2002 ; Vol. 62, No. 2. pp. 528-534.
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