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Invasive and metastatic properties of MCF-7 cells and rasH-transfected MCF-7 cell lines
E P Gelmann1, E W Thompson, C L Sommers
1Division of Medical Oncology, Lombardi Cancer Research Center, Washington, DC 20007.
Abstract:
In vitro invasion and in vivo metastasis assays were performed with a panel of MCF-7 cells transfected with isogenic constructs of mutated rasH genes. Both increased levels of rasH expression and rasH oncogene activation increased activity of derivative cell lines in in vitro invasion assays. In vivo formation of spontaneous metastases was assessed after intradermal inoculation of MCF-7 cells in the vicinity of the mammary fat pads of ovariectomized nude mice. No metastases were seen in the absence of estradiol treatment of the mice. With estradiol supplementation of the mice both the rasH-transfected and control transfected cell lines gave a higher incidence of metastases than parental MCF-7 cells. Prolonged treatment of mice with exogenous estradiol (60 days vs. 21 days) resulted in more frequent metastases to liver and lung at the end of the 90-day observation period. In contrast to activated rasH-gene enhancement of metastatic capacity of rodent fibroblast and epithelial cell lines, there was no correlation of rasH expression with in vivo metastatic capacity of a human mammary carcinoma cell line.
Insights
RasH oncogene activation and estradiol promote breast cancer cell invasion and metastasis in mice. However, RasH expression did not correlate with metastasis in human mammary carcinoma cells, despite estradiol
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- The rasH oncogene plays a role in cell growth and differentiation.
- Estrogen signaling is critical in breast cancer development and progression.
Purpose of the Study:
- To investigate the role of rasH oncogene activation and estradiol in breast cancer cell invasion and metastasis.
- To determine if rasH expression correlates with metastatic capacity in human mammary carcinoma cells.
Main Methods:
- In vitro invasion assays using MCF-7 cells transfected with mutated rasH genes.
- In vivo metastasis assays in ovariectomized nude mice inoculated with MCF-7 cells.
- Assessment of metastasis incidence with and without estradiol supplementation and varying treatment durations.
Main Results:
- Increased rasH expression and activation enhanced in vitro cell invasion.
- Estradiol treatment significantly increased metastasis incidence in vivo.
- Prolonged estradiol treatment led to more frequent liver and lung metastases.
- No correlation was found between rasH expression and in vivo metastatic capacity in the human mammary carcinoma cell line.
Conclusions:
- RasH oncogene activation and estradiol contribute to breast cancer cell metastasis.
- Estradiol is a critical factor for metastasis in this model.
- RasH's role in metastasis may differ between rodent and human cell lines.