title: Analysis of apoptosis-associated molecules Erythroid differentiation regulator 1, bcl-2 and p53 in actinic keratosis after treatment with ingenol mebutate.
abstract: Actinic keratosis (AK) is the most common cutaneous premalignant neoplasm precursor of malignant skin tumors. The aberrant apoptotic pathway is thought to be associated with pathogenesis of AK. Ingenol mebutate has been shown to be effective and safe for treatment of AK. However, the effect of ingenol mebutate on apoptosis-related molecules using human skin samples has not been studied well. Erythroid differentiation regulator 1 (Erdr1) was recently reported to play a crucial role in malignant skin cancers like malignant melanoma. The role of Erdr1 in premalignant actinic keratosis (AK) has not been explored. The purpose of this study was to investigate whether the expression of apoptosis-associated molecules such as Erdr1, p53 and bcl-2 was affected by the treatment of ingenol mebutate in AK. Nine patients with AK underwent skin biopsy at baseline and 8 weeks after treatment with ingenol mebutate for immunohistochemical evaluation with Erdr1, p53 and bcl-2. In addition, skin samples from five control subjects were retrieved. Upregulation of Erdr1 and a significant decrease in expression of p53 and bcl-2 were observed after treatment with ingenol mebutate. Ingenol mebutate treatment for AK resulted in the modulation of apoptosis-associated molecules with an increase in the expression of Erdr1 and a decrease in the expression of p53 and bcl-2.
authors.affiliation: Department of Dermatology, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Yu Ri
authors.identifier: 0000-0003-2903-9534
authors.initials: YR
authors.lastname: Woo
authors.affiliation: Department of Dermatology, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Ji Hong
authors.initials: JH
authors.lastname: Lim
authors.affiliation: Department of Life Science, Sookmyung Women's University, Seoul, Korea.
authors.forename: Seo-Won
authors.initials: SW
authors.lastname: Jeong
authors.affiliation: Institue of Clinical Medical Research, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Dae Ho
authors.initials: DH
authors.lastname: Cho
authors.affiliation: Department of Dermatology, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Hyun Jeong
authors.initials: HJ
authors.lastname: Park
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis; D004224:Diterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D015536:Down-Regulation; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D055623:Keratosis, Actinic / Q000188:drug therapy / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D012189:Retrospective Studies; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C486592:3-ingenyl angelate; D000970:Antineoplastic Agents; D004224:Diterpenes; D008565:Membrane Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C583413:erythroid differentiation regulator 1, human
keywords: actinic keratosis; apoptosis; bcl-2; erythroid differentiation regulator 1; ingenol mebutate; p53