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Steroid regulation of transfected genes in mouse mammary tumour cells
Abstract:
The regulation of mouse mammary tumour virus (MMTV) RNA by glucocorticoid hormones is well-established and has provided much information on how steroid hormones work. However, we have shown that androgens can also control MMTV RNA accumulation in S115 mouse mammary tumour cells. This novel androgen action could be explained on the basis that the MMTV long terminal repeat (LTR) can respond to several classes of steroid if appropriate receptors are present in the cells. We have used transfection experiments to demonstrate that androgens can act directly on the LTR in S115 cells. Hormonal regulation of transfected chimaeric genes into these cells was effected by androgen and glucocorticoid but not by oestrogen or progesterone, corresponding to the receptor status of the cells. Furthermore, hormonal control was also conferred by the LTR on expression of an independent cotransfected adjacent gene under its own separate promoter, suggesting that effects of an LTR can stretch to neighbouring genes in a type of hormone-enhancer insertion mechanism.
Insights
Androgens, not just glucocorticoids, regulate mouse mammary tumour virus (MMTV) RNA. This novel action involves the MMTV long terminal repeat (LTR) directly responding to androgens in S115 cells.
Area of Science:
- Endocrinology
- Molecular Biology
- Virology
Background:
- Glucocorticoid hormones are known regulators of mouse mammary tumour virus (MMTV) RNA.
- Steroid hormone mechanisms are often studied using MMTV as a model system.
Purpose of the Study:
- To investigate the role of androgens in regulating MMTV RNA accumulation.
- To determine if androgens can directly influence the MMTV long terminal repeat (LTR).
Main Methods:
- Transfection experiments in S115 mouse mammary tumour cells.
- Assessing the hormonal regulation of chimaeric genes containing the MMTV LTR.
- Evaluating the effect of the LTR on adjacent gene expression.
Main Results:
- Androgens were shown to control MMTV RNA accumulation in S115 cells.
- Transfection experiments confirmed that androgens act directly on the MMTV LTR.
- The MMTV LTR conferred hormonal regulation by androgens and glucocorticoids, but not oestrogen or progesterone.
- The LTR influenced the expression of an adjacent gene, suggesting a hormone-enhancer insertion mechanism.
Conclusions:
- Androgens represent a novel class of steroid hormones capable of regulating MMTV RNA.
- The MMTV LTR is a key element mediating androgenic control of viral gene expression.
- Hormone-responsive elements within the LTR can influence neighboring genes, expanding the understanding of gene regulation.