Data from Activator Protein-1 Activity Regulates Epithelial Tumor Cell Identity

• DOI: 10.1158/0008-5472.c.6494616.v1
• Publication Date: 2023-03-30T19:13:39Z
• Authors: Michael J. Gerdes; Maxim Myakishev; Nicholas A. Frost; Vikas Rishi; Jaideep Moitra; Asha Acharya; Michelle R. Levy; Sang-won Park; Adam Glick; Stuart H. Yuspa; Charles Vinson
• Keywords: Transdifferentiation; Chromatin immunoprecipitation; Beta-catenin

<div>Abstract<p>To examine the consequences of inhibiting activator protein-1 (AP-1) transcription factors in skin, transgenic mice were generated, which use tetracycline system to conditionally express A-FOS, a dominant negative that inhibits AP-1 DNA binding. Older develop mild alopecia and hyperplasia sebaceous glands, particularly around eyes. When A-FOS was expressed during chemical-induced skin carcinogenesis, do not characteristic benign malignant squamous lesions but instead adenomas containing signature mutation <i>H-ras</i> proto-oncogene. Inhibiting activity after tumor formation caused tumors transdifferentiate into tumors. Furthermore, reactivating results reciprocal transdifferentiation In both cases transdifferentiation, individual cells molecular markers for cell types, indicating have capacity multiple lineages. Molecular characterization cultured keratinocytes material indicates regulates balance between wnt/β-catenin hedgehog signaling pathways determine lineages, respectively. Chromatin immunoprecipitation analysis c-Jun binds several wnt promoters, are misregulated by expression, suggesting members pathway can be primary targets transcriptional regulation. Thus, lineage is essential maintain identity. (Cancer Res 2006; 66(15): 7578-88)</p></div>