Carcinogenesis, Vol 19, 833-839, Copyright © 1998 by Oxford University Press
JJ Li, NH Colburn and LW Oberley
We have reported the tumor suppressive effects of manganese-containing
superoxide dismutase (MnSOD) in human breast cancer cells. In order to
understand the molecular mechanism of this anti-tumor effect, we asked
whether tumor suppressor gene(s), especially the ones inhibiting tumor
invasion and motility, are involved in MnSOD-induced tumor suppression.
Maspin is one of the serpin family of protease inhibitors that has been
shown to function as a tumor-suppressor in human breast epithelium. In the
present study, we demonstrated that maspin expression was up- regulated in
human breast cancer MCF-7 cells that overexpress a normal MnSOD gene. The
induced maspin transcripts were detected by RT-PCR and Northern blot and
identified by sequencing. Maspin gene expression was induced in parallel
with the level of exogenous MnSOD protein, which was induced by
transfection with varied amounts of cDNA. In order to analyze cell invasion
ability, which may be related to the induced maspin gene expression, MnSOD
stable transfectants were tested using a matrigel invasion chamber. The
invasion ability was reduced to 24% and 36% in the cloned (MCF + SOD) and
pooled MnSOD-transfectants (MCF + SODp) respectively, compared with the
wild-type MCF-7 cell line. In conclusion, these results suggest that
overexpression of a normal MnSOD cDNA in human breast cancer cells
up-regulates the gene expression of the protease inhibitor, maspin, which
may play a role in the inhibitory function of MnSOD on tumor invasion.
ARTICLES
Maspin gene expression in tumor suppression induced by overexpressing manganese-containing superoxide dismutase cDNA in human breast cancer cells
Gene Regulation Section, Laboratory of Biochemical Physiology, National Cancer Institute, NCI-FCRDC, Frederick, MD 21702-1201, USA. Lij@ncifcrf.gov
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