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Molecular cloning and functional analysis of a novel cadmium-responsive proto-oncogene.

Authors
Joseph-P; Lei-Y; Whong-W; Ong-T
Source
Cancer Res 2002 Feb; 62(3):703-707
NIOSHTIC No.
20022325
Abstract
The molecular mechanisms potentially responsible for cell transformation and tumorigenesis induced by cadmium, a human carcinogen, were investigated by differential gene expression analysis of BALB/c-3T3 cells transformed with cadmium chloride (CdCl(2)). Differential display analysis of gene expression revealed consistent overexpression of mouse translation initiation factor 3 (TIF3; GenBank accession number AF271072) in the cells transformed with CdCl(2) when compared with nontransformed cells. The predicted protein encoded by TIF3 cDNA exhibited 99% similarity to human eukaryotic initiation factor 3 p36 protein. A M(r) 36,000 protein was detected in cells transfected with an expression vector containing TIF3 cDNA. Transfection of NIH3T3 cells with an expression vector containing TIF3 cDNA resulted in overexpression of the encoded protein, and this was associated with cell transformation, as evidenced by the appearance of transformed foci exhibiting anchorage-independent growth on soft agar and tumorigenic potential in nude mice. Expression of the antisense RNA against TIF3 mRNA resulted in significant reversal of oncogenic potential of the CdCl(2)-transformed BALB/c-3T3 cells. Taken together, these findings demonstrate for the first time that the cell transformation and tumorigenesis induced by CdCl(2) are due, at least in part, to the overexpression of TIF3, a novel cadmium-responsive proto-oncogene.
Keywords
Molecular-biology; Cell-transformation; Tumorigenesis; Cadmium-dust; Cadmium-compounds; Carcinogens; Ribonucleic-acids; Oncogenic-agents
Contact
MS 3014, Toxicology and Molecular Biology Branch, National Institute for Occupational Safety and Health, 1095 Willowdale Rd., Morgantown, WV 26505
CODEN
CNREA8
CAS No.
10108-64-2
Publication Date
20020201
Document Type
Journal Article
Email Address
pcj5@cdc.gov
Fiscal Year
2002
NTIS Accession No.
NTIS Price
Issue of Publication
3
ISSN
0008-5472
NIOSH Division
HELD
Priority Area
Research Tools and Approaches: Cancer Research Methods
Source Name
Cancer Research
State
WV
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