Related Experiment Videos
Androgen stimulates mitogen-activated protein kinase in human breast cancer cells
Abstract:
The mechanisms by which androgens modulate breast cancer cell growth are largely unknown. Using cultured human PMC42 breast cancer cells, we have determined effects of the androgen R1881 on the activity of the mitogen-activated protein kinases extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 kinase. R1881 did not alter JNK and p38 kinase activity, but activated ERK in a dose-dependent manner. Activation was rapid, peaking at 5 min followed by a decline to baseline after 30-60 min, and was accompanied by tyrosine phosphorylation of ERK. The androgen antagonist flutamide elevated ERK to similar levels and DNA synthesis to levels half those seen with R1881; in addition, excess flutamide lowered R1881-stimulated DNA synthesis to levels seen with flutamide alone. These findings suggest (i) that in human PMC42 breast cancer cells R1881 activates ERK through a non-genomic mechanism, (ii) that this non-genomic mechanism is equivalently activated by the androgen antagonist flutamide, and (iii) that androgen/antiandrogen effect on DNA synthesis may involve both genomic and non-genomic mechanisms. These findings may have important implications for the clinical use of such agents in breast cancer.
Insights
Androgens rapidly activate extracellular signal-regulated kinase (ERK) in breast cancer cells via a non-genomic pathway. This activation, along with DNA synthesis, may involve both genomic and non-genomic mechanisms, impacting cancer treatment strategies.
Area of Science:
- Endocrinology
- Molecular Biology
- Cancer Research
Background:
- Mechanisms of androgen action in breast cancer cell growth remain unclear.
- Androgens are implicated in various cancer types, necessitating a deeper understanding of their cellular effects.
Purpose of the Study:
- To investigate the effects of the androgen R1881 on mitogen-activated protein kinase (MAPK) pathways in human breast cancer cells.
- To elucidate the signaling mechanisms underlying androgen-mediated breast cancer cell proliferation.
Main Methods:
- Cultured human PMC42 breast cancer cells were treated with R1881.
- Activity of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 kinase was measured.
- Effects of androgen antagonist flutamide on ERK and DNA synthesis were assessed.
Main Results:
- R1881 dose-dependently activated ERK, with rapid kinetics (peak at 5 min) and tyrosine phosphorylation.
- JNK and p38 kinase activities were not altered by R1881.
- Flutamide also elevated ERK and DNA synthesis, and partially inhibited R1881-stimulated DNA synthesis.
Conclusions:
- R1881 activates ERK in PMC42 cells through a non-genomic mechanism.
- The androgen antagonist flutamide activates this non-genomic ERK pathway.
- Androgen and antiandrogen effects on DNA synthesis likely involve both genomic and non-genomic pathways, with clinical implications for breast cancer therapy.