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Negative growth regulation of oncogene-transformed mammary epithelial cells by tumor inhibitors
N T Telang1, S Inoue, H L Bradlow
1Strang-Cornell Cancer Research Laboratory, Cornell University Medical College, New York, New York, USA.
Abstract:
Deregulated expression of Ras and myc oncogenes confers neoplastic transformation in non-tumorigenic mammary epithelial cells. Down-regulation of perturbed biomarkers prior to tumorigenesis may provide a means of effective chemoprevention. In vitro experiments were designed to i) identify specific molecular, endocrine and cellular biomarkers as quantitative end points for preneoplastic transformation, and ii) utilize these end points to evaluate chemopreventive efficacy of selected naturally-occurring and synthetic tumor inhibitors. Stable Ras and myc transfectants exhibited persistent expression of oncogene specific mRNA transcripts, altered estradiol biotransformation and enhanced anchorage-independent growth in vitro prior to tumorigenesis in vivo. Treatment of the transfectants with omega-3-fatty acid, indole-3-carbinol and tamoxifen individually suppressed the perturbed molecular, endocrine and cellular biomarkers in vitro. Thus, suppressed oncogene expression and altered estrogen metabolism may be important determinants for antiproliferative mechanisms in mammary tumor inhibition, providing useful end points for chemopreventive intervention of preneoplasia.
Insights
Chemoprevention strategies can target preneoplastic mammary cells by suppressing oncogene expression and altering estrogen metabolism. Naturally occurring and synthetic compounds show promise in down-regulating key biomarkers.
Area of Science:
- Oncology
- Molecular Biology
- Endocrinology
Background:
- Deregulated Ras and myc oncogenes drive neoplastic transformation in mammary epithelial cells.
- Identifying biomarkers for preneoplastic transformation is crucial for effective chemoprevention.
Purpose of the Study:
- Identify molecular, endocrine, and cellular biomarkers for preneoplastic mammary cell transformation.
- Evaluate the chemopreventive efficacy of natural and synthetic tumor inhibitors using these biomarkers.
Main Methods:
- Utilized stable Ras and myc transfectants of mammary epithelial cells.
- Quantified oncogene-specific mRNA, estradiol biotransformation, and anchorage-independent growth.
- Assessed the effects of omega-3 fatty acid, indole-3-carbinol, and tamoxifen on these biomarkers.
Main Results:
- Ras and myc transfectants showed persistent oncogene expression, altered estradiol metabolism, and enhanced growth prior to tumorigenesis.
- Treatment with omega-3 fatty acid, indole-3-carbinol, and tamoxifen suppressed these perturbed biomarkers in vitro.
Conclusions:
- Suppressed oncogene expression and altered estrogen metabolism are key antiproliferative mechanisms in mammary tumor inhibition.
- These biomarkers serve as valuable end points for chemopreventive intervention against preneoplasia.