Inhibition of cell growth by overexpression of manganese superoxide dismutase (MnSOD) in human pancreatic carcinoma.
Manganese superoxide dismutase (MnSOD) levels have been found to be low in human pancreatic cancer [Pancreas 26, (2003), 23] and human pancreatic cancer cell lines [Cancer Res. 63, (2003), 1297] when compared to normal human pancreas. We hypothesized that stable overexpression of pancreatic cancer cells with MnSOD cDNA would alter the malignant phenotype. MIA PaCa-2 cells were stably transfected with a pcDNA3 plasmid containing sense human MnSOD cDNA or containing no MnSOD insert by using the lipofectAMINE method. G418-resistant colonies were isolated, grown and maintained. Overexpression of MnSOD was confirmed in two selected clones with a 2-4-fold increase in MnSOD immunoreactive protein. Compared with the parental and neo control cells, the MnSOD-overexpressing clones had decreased growth rates, growth in soft agar and plating efficiency in vitro, while in vivo, the MnSOD-overexpressing clones had slower growth in nude mice. These results suggest that MnSOD may be a tumor suppressor gene in human pancreatic cancer.
Ough
Matthew
M
University of Iowa College of Medicine, Iowa City, IA, USA.
Lewis
Anne
A
Zhang
Yuping
Y
Hinkhouse
Marilyn M
MM
Ritchie
Justine M
JM
Oberley
Larry W
LW
Cullen
Joseph J
JJ
D000362:Agar; D000368:Aged; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000235:genetics; D001728:Dicumarol / Q000494:pharmacology; D015870:Gene Expression / Q000528:radiation effects; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D014162:Transfection
D000975:Antioxidants; D018076:DNA, Complementary; D013481:Superoxides; D001728:Dicumarol; D000362:Agar; D013482:Superoxide Dismutase