Related Experiment Videos
Modulation of estrogen receptor by insulin and its biologic significance
Abstract:
It has been proposed that a nonsteroidal hormone such as insulin may directly exert an influence through estrogen receptors and alter the biologic behavior of steroid hormone target tissue. The implication of such a proposal is that diabetes may alter the outcome of estrogen receptor-positive tumors such as breast or endometrial carcinomas. To evaluate the effect of insulin on a receptor-positive tumor, we examined the direct effect of insulin on an estrogen receptor and its subsequent biologic effect on a receptor-positive endometrial carcinoma model in vitro and in vivo. An in vitro experiment demonstrated that when the estrogen receptor-positive cell line was grown in serum-free media with low insulin, there was a loss of intracellular receptors for estrogen. This loss of estrogen receptors was also associated with increased growth rate as reflected by increased thymidine uptake. Similarly, in vivo experiments demonstrated that a diabetic host with a high blood glucose level and a low insulin level exhibited development of growth of a receptor-negative tumor with accelerated growth rate in contrast to growth of a receptor-positive tumor with slower growth rate in a normal host with normal serum insulin and blood glucose levels. Data suggest that insulin may modulate the growth of estrogen receptor-positive tumors through its direct effect on estrogen receptors.
Insights
Diabetes may impact estrogen receptor-positive tumors. Low insulin levels in diabetic models led to reduced estrogen receptors and accelerated tumor growth, suggesting insulin modulates tumor behavior.
Area of Science:
- Endocrinology
- Oncology
- Molecular Biology
Background:
- Nonsteroidal hormones like insulin may influence estrogen receptors.
- Diabetes could alter outcomes for estrogen receptor-positive cancers.
Purpose of the Study:
- To investigate insulin's direct effect on estrogen receptors.
- To evaluate insulin's impact on estrogen receptor-positive endometrial carcinoma growth.
Main Methods:
- In vitro: Estrogen receptor-positive cell lines cultured with varying insulin levels.
- In vivo: Diabetic and normal host models with implanted tumors.
- Assessed intracellular estrogen receptors and tumor growth (thymidine uptake).
Main Results:
- Low insulin in vitro caused loss of intracellular estrogen receptors and increased cell growth.
- In vivo, diabetic hosts showed accelerated growth of receptor-negative tumors compared to slower growth in normal hosts.
- Diabetic hosts exhibited a shift towards receptor-negative tumor characteristics.
Conclusions:
- Insulin may directly modulate estrogen receptor levels.
- Insulin's effect on estrogen receptors could influence the growth of estrogen receptor-positive tumors.
- Findings suggest a link between diabetes, insulin, and cancer progression.