Abstract B12: Expression of Integrated Stress Response proteins during the progression of UVB-induced squamous cell carcinoma

The major environmental risk factor for developing non-melanoma skin cancers (NMSCs) is exposure to the ultraviolet-B (UVB) wavelengths found in sunlight. Unlike other types of cancer where the occurrence each year is precisely known, so many NMSCs occur each year in the United States that the incidence of NMSC is not accurately reported. Treatment of NMSC costs the U.S. healthcare system over 1 billion dollars annually. Therefore while NMSC is rarely lethal, the expense of NMSC treatment is the fifth highest among all cancer treatments. In response to a myriad of environmental stresses, including UVB irradiation, eukaryotic cells rapidly modulate protein synthesis. An important mechanism for translation regulation involves phosphorylation of the α subunit of eukaryotic initiation factor 2 (eIF2α), which results in a prompt decrease in global protein synthesis, concurrent with preferential translation of cytoprotective gene transcripts. Because a range of different stresses can activate one of four eIF2 kinases, this pathway is referred to as the Integrated Stress Response (ISR). Although the ISR pathway has been implicated in carcinogenesis in a variety of tissues, little is known about whether the ISR can modulate the development of NMSC in human skin. We previously defined the cytoprotective role of the ISR in response to UVB-irradiation of human keratinocytes in vitro. Following UVB exposure, keratinocytes lacking an ISR response have a shortened G1 arrest, a decreased ...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Translation Control: an Adaptive Response to Oncogenic Cellular Stress Source Type: research