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Balance between activated-STAT and MAP kinase regulates the growth of human bladder cell lines after treatment with
H Kawamata1, K Hattori, F Omotehara
1Second Department of Oral and Maxillofacial Surgery, Tokushima University School of Dentistry, Tokushima 770-8504, Japan.
Abstract:
Epidermal growth factor (EGF) is a potent mitogen, and its action is mediated by MAP kinase (MAPK). Reportedly EGF activates STAT, induces the expression of p21waf1, and subsequently inhibits the growth of several types of cancer cells. In this study, we used human bladder cancer cells (T24 and RT4), immortalized non-tumorigenic human urothelial cells (1T-1, 1T-2, and 1T-3), and epidermal carcinoma cells (A431). EGF inhibited the growth of T24 and A431, and stimulated the growth of 1T-1, 1T-3 and 1T-2, but did not affect the growth of RT4. EGF activated MAPK strongly in 1T-1, and slightly in A431, T24, 1T-2, and 1T-3 but marginally in RT4. We detected the activation of STAT in T24, 1T-3 and A431 after EGF treatment. EGF enhanced the expression of p21waf1 mRNA in T24, 1T-2, 1T-3 and A431, and activated the p21waf1 promoter in T24 cells. These results suggest that i) EGF inhibits the growth of T24 cells via induction of p21waf1 mediated by STAT, and ii) the balance between the STAT-induced p21waf1 and MAPK activities regulates the growth of human bladder cells after EGF treatment.
Insights
Epidermal growth factor (EGF) impacts human cell growth differently. EGF inhibits T24 bladder cancer cell growth by inducing p21waf1 via STAT, while balancing STAT and MAPK pathways regulates urothelial cell growth.
Area of Science:
- Cell Biology
- Molecular Biology
- Cancer Research
Background:
- Epidermal growth factor (EGF) is a known mitogen.
- EGF's action involves MAP kinase (MAPK) signaling.
- EGF has been reported to activate STAT and induce p21waf1, potentially inhibiting cancer cell growth.
Purpose of the Study:
- To investigate the differential effects of EGF on human bladder cancer cells and urothelial cells.
- To elucidate the roles of STAT and MAPK pathways in EGF-mediated cell growth regulation.
- To examine the induction of p21waf1 expression by EGF in various cell lines.
Main Methods:
- Utilized human bladder cancer cell lines (T24, RT4), immortalized urothelial cell lines (1T-1, 1T-2, 1T-3), and epidermal carcinoma cells (A431).
- Assessed EGF's effect on cell growth, MAPK activation, STAT activation, and p21waf1 mRNA expression.
- Investigated EGF's impact on the p21waf1 promoter activity in T24 cells.
Main Results:
- EGF inhibited growth in T24 and A431 cells, stimulated growth in 1T-1, 1T-3, and 1T-2 cells, and had no effect on RT4 cells.
- MAPK activation varied across cell lines, being strongest in 1T-1 and marginal in RT4.
- STAT activation was detected in T24, 1T-3, and A431 cells; EGF enhanced p21waf1 mRNA expression in T24, 1T-2, 1T-3, and A431 cells.
Conclusions:
- EGF inhibits T24 bladder cancer cell growth through STAT-mediated induction of p21waf1.
- The balance between STAT-induced p21waf1 and MAPK activity is critical for regulating human bladder cell growth following EGF treatment.