Expression and regulation of a molecular marker, SPR1, in multistep bronchial carcinogenesis

Derick H Lau, Ling Xue, Ruide Hu, Thomas Liaw, Reen Wu, Sekhar Reddy

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Abstract

A small proline-rich protein, SPR1, is overexpressed in squamous metaplasia of bronchial epithelium. We studied the expression and regulation of SPR1 in a series of human bronchial epithelial cell lines representing a model of multistep bronchial carcinogenesis. These cell lines included a primary culture of tracheobronchial epithelial cells (HTBE), a papilloma virus-transformed tracheobronchial epithelial cell line (HBE1), a cell line selected from HBE1 by a tobacco carcinogen and a phorbol ester (HBE1-C), a simian virus-transformed bronchial epithelial cell line (BEAS-2B), and a lung carcinoma cell line (H460). Different tumorigenic potentials of these cell lines were indicated by graded levels of telomerase activity. Concomitant with squamous transformation, there was an increase in SPR1 expression in HTBE, HBE1, and HBE1-C that was reversible by vitamin A. With progression of tumorigenicity, there was a marked reduction in SPR1 expression in BEAS-2B and a total loss of expression in H460. In these latter cell lines representing advanced malignant transformation, there was a loss of up- and downregulation, respectively, by the phorbol ester and vitamin A. Transfection study with chimeric constructs of the SPR1 promoter and a reporter gene showed that the dysregulation of SPR1 expression in malignant transformation was a result of perturbation of the basal and enhancer elements of the first 162 nucleotides in the 5'-flanking promoter region of the SPR1 gene. These findings suggest an association of transcriptional dysregulation of the SPR1 gene with multistep bronchial carcinogenesis.

Original languageEnglish (US)
Pages (from-to)92-96
Number of pages5
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume22
Issue number1
StatePublished - 2000

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Carcinogenesis
Cells
Cell Line
Genes
Phorbol Esters
Vitamin A
Viruses
Epithelial Cells
Tobacco
Telomerase
Cell culture
Genetic Promoter Regions
Proline
Carcinogens
Nucleotides
Association reactions
5' Flanking Region
Metaplasia
Papilloma
Reporter Genes

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology

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Expression and regulation of a molecular marker, SPR1, in multistep bronchial carcinogenesis. / Lau, Derick H; Xue, Ling; Hu, Ruide; Liaw, Thomas; Wu, Reen; Reddy, Sekhar.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 22, No. 1, 2000, p. 92-96.

Research output: Contribution to journalArticle

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