The Role of Protein Tyrosine Kinase 6 in UVB-Induced Signaling and Skin Carcinogenesis
thesisposted on 10.03.2017, 00:00 by Michael I. Chastkofsky
Protein Tyrosine Kinase 6 (PTK6) belongs to a small family of Src-related nonmyristoylated intracellular tyrosine kinases and is involved in normal epithelial homeostasis and cancer. PTK6 is expressed in the stratified squamous epithelium of the skin in the differentiated suprabasal cell layer, and its expression is induced by differentiation. PTK6 expression is also induced by stress and DNA damage. We treated carcinogen-sensitive wild-type and Ptk6-null SENCAR mice with incremental doses of UV-B over time to induce tumorigenesis and identify the contribution of PTK6. Ptk6+/+ mice developed more tumors at a faster rate than Ptk6-/- mice. Ptk6+/+ mice were also more sensitive to UVR than Ptk6-/- mice and exhibited greater activation of STAT3, FAK, and BCAR1. Ptk6+/+ mice developed a greater tumor load more rapidly than Ptk6-/- mice. PTK6 did not directly promote proliferation, but was strongly expressed and activated in invasive basal cells.