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Cancer Types / Pediatric Cancers / Retinoblastoma / NCI Resources
National Cancer Institute®
Last Modified: June 1, 2002
1
UI - 8548579
AU - Hanania EG; Au WW; Ullrich RL; Papaconstantinou J
TI -
Regulation of retinoblastoma gene expression in a mouse mammary tumor
model.
SO - Cancer Gene Ther 1995 Dec;2(4):251-61
AD - Department of Human Biological Chemistry and Genetics, University of
Texas Medical Branch, Galveston 77555, USA.
We initiated studies to investigate the involvement of the murine
retinoblastoma (RB) gene in mammary carcinogenesis using cell lines
derived from mammary glands of irradiated mice. We found that the RB
mRNA levels as well as the amounts of the nuclear phosphoprotein were
significantly reduced as the cells progressed in vitro from
non-tumorigenic to tumorigenic stages. To further investigate RB gene
expression with cellular development and tumorigenicity, we transfected
malignant cells with expression vectors containing the murine RB cDNA
driven by either the SV40 or the mouse metallothionein promoter
sequences. The neomycin resistant gene was included in both vectors and
was used as a selective marker for the transfected cells. Cells with
reduced levels of endogenous RB mRNA were stably transfected and showed
increased expression of RB. In addition, the morphology of these cells
were altered and their growth rates in culture were reduced. Injection
of the transfected cells into host mice resulted in a delayed onset of
tumors compared with nontransfected parental cells. Our studies provide
experimental data to confirm that loss of RB gene activity is involved
in neoplastic transformation of cells and support the multistep theory
of carcinogenesis.
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