Related Experiment Videos
Laminin inhibits estrogen action in human breast cancer cells
T L Woodward1, H Lu, S Z Haslam
1Department of Physiology, Michigan State University, East Lansing 48824-1101, USA.
Abstract:
Breast tumors that lack estrogen responsiveness have a poor prognosis. Despite the critical importance to breast cancer treatment, little is known about the loss of estrogen responsiveness and the development of antiestrogen resistance. We have examined the regulation of estrogen-induced proliferation, estrogen regulation of progesterone receptor (PR) expression, and estrogen signaling pathways in estrogen receptor (ER) positive (MCF-7 and T47D) breast cancer cell lines by specific extracellular matrix proteins (ECM) under serum-free conditions. Estrogen, supplemented with submaximal concentrations of insulin-like growth factor I (IGF-I) and epidermal growth factor (EGF), stimulated DNA synthesis of MCF-7 cells 7- to 10-fold and T47D cells 2-fold on collagen I or fibronectin. However, estrogen-induced proliferation was greatly reduced on laminin. In contrast, IGF-I or EGF, alone, stimulated proliferation of MCF-7 and T47D cells on all ECM. Thus, ER+ breast cancer cells were not refractory to mitogens when cultured on laminin. Similarly, estrogen induction of PR occurred on fibronectin or collagen I, but not on laminin. While ER content was similar on all ECM, estrogen stimulation of estrogen response element (ERE)-luciferase activity was significantly lower in MCF-7 cells cultured on laminin. Therefore, changes in ECM composition that occur in breast cancer may alter estrogen-responsiveness and the effectiveness of antiestrogen therapies in ER+ breast cancer cells.
Insights
Extracellular matrix proteins influence estrogen responsiveness in breast cancer cells. Laminin reduces estrogen-induced proliferation and progesterone receptor expression, impacting antiestrogen therapy effectiveness.
Area of Science:
- Oncology
- Cell Biology
- Biochemistry
Background:
- Estrogen receptor-positive (ER+) breast tumors lacking estrogen responsiveness have a poor prognosis.
- Understanding the mechanisms behind antiestrogen resistance is crucial for effective breast cancer treatment.
- The role of extracellular matrix (ECM) proteins in regulating estrogen responsiveness remains largely unexplored.
Purpose of the Study:
- To investigate how specific ECM proteins affect estrogen-induced proliferation, progesterone receptor (PR) expression, and estrogen signaling in ER+ breast cancer cells.
- To determine if ECM composition influences the response of breast cancer cells to mitogens like insulin-like growth factor I (IGF-I) and epidermal growth factor (EGF).
- To elucidate the impact of ECM on estrogen signaling pathways, including estrogen response element (ERE) activity.
Main Methods:
- Culturing ER+ breast cancer cell lines (MCF-7 and T47D) on different ECM proteins (collagen I, fibronectin, laminin) under serum-free conditions.
- Assessing estrogen-induced DNA synthesis and proliferation in response to estrogen, IGF-I, and EGF.
- Measuring estrogen receptor (ER) content and estrogen induction of PR expression.
- Quantifying estrogen signaling by measuring ERE-luciferase activity.
Main Results:
- Estrogen, with IGF-I and EGF, stimulated proliferation on collagen I and fibronectin but significantly less on laminin.
- IGF-I or EGF alone stimulated proliferation on all tested ECM, indicating cells were not refractory to mitogens on laminin.
- Estrogen induction of PR expression occurred on fibronectin and collagen I, but not on laminin.
- ERE-luciferase activity was significantly lower in MCF-7 cells cultured on laminin compared to other ECMs, despite similar ER content.
Conclusions:
- Specific ECM proteins, particularly laminin, can significantly reduce estrogen responsiveness in ER+ breast cancer cells.
- Altered ECM composition in breast tumors may contribute to the development of antiestrogen resistance.
- These findings highlight the potential for ECM-targeted therapies to improve the effectiveness of antiestrogen treatments in breast cancer.