Am. J. Respir. Cell Mol. Biol.,
Volume 22, Number 1, January, 2000 92-96
Expression and Regulation of a Molecular Marker, SPR1, in
Multistep Bronchial Carcinogenesis
Derick
Lau,
Ling
Xue,
Ruide
Hu,
Thomas
Liaw,
Reen
Wu,
and
Sekhar
Reddy*
University of California, Davis Cancer Center; and Veterans Administration Northern California Health Care System,
Sacramento, California
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.
*
Current address: The Johns Hopkins School of Public Health, Dept. of
Environmental Health Sciences, Div. of Physiology, Rm. W7006, 615 N. Wolfe St., Baltimore, MD 21205.
