Balance between activated-STAT and MAP kinase regulates the growth of human bladder cell lines after treatment with epidermal growth factor.
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.
Kawamata
H
H
Second Department of Oral and Maxillofacial Surgery, Tokushima University School of Dentistry, Tokushima 770-8504, Japan.
Hattori
K
K
Omotehara
F
F
Uchida
D
D
Hino
S
S
Sato
M
M
Oyasu
R
R
D015152:Blotting, Northern; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000096:biosynthesis; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis; D012045:Regulatory Sequences, Nucleic Acid / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050794:STAT1 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects; D015534:Trans-Activators / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects; D001743:Urinary Bladder / Q000166:cytology / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D020928:Mitogen-Activated Protein Kinases