v-Ha-ras mitogenic signaling through superoxide and derived reactive oxygen species

Ji-Qin Yang; Garry R Buettner; Frederick E Domann; Qiang Li; John F Engelhardt; Christine Darby Weydert; Larry W Oberley

doi:10.1002/mc.10037

Back

v-Ha-ras mitogenic signaling through superoxide and derived reactive oxygen species

Journal article

Peer reviewed

v-Ha-ras mitogenic signaling through superoxide and derived reactive oxygen species

Ji-Qin Yang, Garry R Buettner, Frederick E Domann, Qiang Li, John F Engelhardt, Christine Darby Weydert and Larry W Oberley

Molecular carcinogenesis, Vol.33(4), pp.206-218

04/2002

DOI: 10.1002/mc.10037

PMID: 11933074

View Online

Abstract

The ras proto-oncogene is frequently mutated in human tumors and functions to constitutively stimulate signal transduction cascades, resulting in unchecked proliferation and malignant transformation. In certain cells, superoxide functions as a signal-transduction messenger, mediating the downstream effects of ras and rac. We demonstrated previously that v-Ha-ras-transfected rat kidney epithelial cells (RECs) overproduced superoxide anion and that this superoxide production was mediated by ras. In the present study, we further demonstrated that v-Ha-ras overexpression transformed immortal nonmalignant RECs into malignant cancer cells; v-Ha-ras-transfected cells formed clones in soft agar, had high plating efficiency, and formed tumors in nude mice. Our data suggest that superoxide radical plays a role in ras-induced transformation; modulation of intracellular superoxide level by overexpression of manganese-containing superoxide dismutase or copper- and zinc-containing superoxide dismutase inhibited ras-induced transformation, as evidenced by in vitro studies of plating efficiency and by in vivo studies of tumor formation in nude mice. Overexpression of catalase (CAT) alone was found to have little effect on tumor cell growth, but overexpression of glutathione peroxidase 1 (GPx1) completely suppressed tumor cell growth in nude mice. This finding suggests that peroxides removed by GPx1, but not by CAT, are also involved in ras-induced transformation.

Transfection

Recombinant Proteins - metabolism

Cell Line

Superoxide Dismutase - genetics

Reactive Oxygen Species - metabolism

Catalase - genetics

Glutathione Transferase - metabolism

Rats

NF-kappa B - metabolism

Transcription Factor AP-1 - metabolism

Kidney

Oncogene Protein p21(ras) - metabolism

Catalase - metabolism

Animals

Glutathione Transferase - genetics

Cell Division

Superoxides - metabolism

Signal Transduction - physiology

Colony-Forming Units Assay

Mitogens - physiology

Genes, ras

Superoxide Dismutase - metabolism

Oncogene Protein p21(ras) - genetics

Urothelium

Details

Title: Subtitle: v-Ha-ras mitogenic signaling through superoxide and derived reactive oxygen species
Creators: Ji-Qin Yang - Free Radical and Radiation Biology Program, Department of Radiation Oncology, B180 Medical Laboratories, University of Iowa, Iowa City, Iowa, USA
Garry R Buettner
Frederick E Domann
Qiang Li
John F Engelhardt
Christine Darby Weydert
Larry W Oberley
Resource Type: Journal article
Publication Details: Molecular carcinogenesis, Vol.33(4), pp.206-218
Publisher: United States
DOI: 10.1002/mc.10037
PMID: 11933074
ISSN: 0899-1987
eISSN: 1098-2744
Grant note: CA66081 / NCI NIH HHS
Language: English
Date published: 04/2002
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Anatomy and Cell Biology; Pathology; Surgery; Radiation Oncology; Internal Medicine
Record Identifier: 9984025431602771

Metrics

12 Record Views

44 Times Cited - Web of Science

See more details