Abstract 3591: The role of T-cell protein tyrosine phosphatase (TC-PTP) in UVB-induced epidermal cell proliferation and survival.

Abstract

Abstract Ultraviolet (UV) radiation is the primary cause of human skin cancer. Signal transducer and activator of transcription 3 (Stat3) is one of the key regulators of epidermal cell survival and proliferation during the development of UV-induced skin cancer. We have previously shown that T-cell protein tyrosine phosphatase (TC-PTP) contributes to the rapid dephosphorylation /deactivation of Stat3 in response to UVB irradiation in keratinocytes. In the current work, we investigated the functional role of TC-PTP in keratinocyte survival and proliferation following UVB exposure. Knockdown of TC-PTP in mouse keratinocytes using siRNA significantly reduced apoptosis following UVB irradiation in comparison with control keratinocytes as evidenced by the decreased levels of activated caspase-3 and PARP cleavage. This reduction corresponded with an increased level of phososphorylated Stat3 in TC-PTP-deficient keratinocytes. Knockdown of TC-PTP in keratinocytes also significantly increased cell proliferation following UVB irradiation compared with control keratinocytes. Similar with these results, overexpression of TC-PTP in keratinocytes significantly increased apoptosis and decreased cell proliferation in response to UVB irradiation compared with control keratinocytes, which corresponded with a decreased level of phosphorylated Stat3. Further studies using TC-PTP-deficient keratinocyte cell lines showed that cell viability was increased in TC-PTP-deficient cells following UVB irradiation. Treatment of TC-PTP-deficient keratinocytes with specific Stat3 inhibitor, STA21 significantly reduced cell viability, upon UVB exposure in comparison with untreated TC-PTP-deficient keratinocytes, which suggests that the effect of TC-PTP on cell viability is mediated by Stat3 dephosphorylation. Combined, our results indicated that TC-PTP plays an important role in the regulation of keratinocyte proliferation and survival after UVB exposure via modulation of Stat3 signaling. Furthermore, these results suggest that TC-PTP may be a novel potential target for the prevention of UVB-induced skin cancer. Citation Format: Young S. Lee, Jun W. Shin, Liza D. Morales, Thomas J. Slaga, Dae J. Kim. The role of T-cell protein tyrosine phosphatase (TC-PTP) in UVB-induced epidermal cell proliferation and survival. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3591. doi:10.1158/1538-7445.AM2013-3591