Protein Tyrosine Kinase 6 Regulates UVB-Induced Signaling and Tumorigenesis in Mouse Skin.
Protein tyrosine kinase 6 (PTK6, also called BRK) is an intracellular tyrosine kinase expressed in the epithelial linings of the gastrointestinal tract and the skin, where it is expressed in nondividing differentiated cells. We found that PTK6 expression increases in the epidermis following UVB treatment. To evaluate the roles of PTK6 in the skin following UVB-induced damage, we exposed back skin of Ptk6 +/+ and Ptk6 -/- SENCAR mice to incremental doses of UVB for 30 weeks. Wild-type mice were more sensitive to UVB and exhibited increased inflammation and greater activation of signal transducer and activator of transcription-3 (STAT3) than Ptk6-/- mice. Disruption of Ptk6 did not have an impact on proliferation, although PTK6 was expressed and activated in basal epithelial cells in wild-type mice following UVB treatment. However, wild-type mice exhibited shortened tumor latency and increased tumor load compared with Ptk6-/- mice, and STAT3 activation was increased in these tumors. PTK6 activation was detected in UVB-induced tumors, and this correlated with increased activating phosphorylation of focal adhesion kinase (FAK) and breast cancer anti-estrogen resistance 1 (BCAR1). Activation of PTK6 was also detected in human squamous cell carcinomas of the skin. Although PTK6 has roles in normal differentiation, it also contributes to UVB-induced injury and tumorigenesis in vivo.
Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA; Department of Oral Sciences, College of Dentistry, University of Illinois at Chicago, Chicago, Illinois, USA.
Michael I
MI
Chastkofsky
Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA.
Wenjun
W
Bie
Global Path Imaging and Consulting, Metamora, Illinois, USA.
Susan M
SM
Ball-Kell
Section of Dermatology, Department of Medicine, University of Chicago, Chicago, Illinois, USA.
Yu-Ying
YY
He
Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA. Electronic address: atyner@uic.edu.
Angela L
AL
Tyner
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001707:Biopsy, Needle; D063646:Carcinogenesis / Q000235:genetics* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D049109:Cell Proliferation / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018632:Mice, Inbred SENCAR; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects*; D011897:Random Allocation; D012016:Reference Values; D015398:Signal Transduction; D012867:Skin / Q000473:pathology* / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects*
D011505:Protein-Tyrosine Kinases; C000598269:Ptk6 protein, mouse