RRC ID 63005
著者 Morita N, Onodera S, Nakamura Y, Nakamura T, Takahashi SI, Nomura T, Azuma T.
タイトル Keratinocytes from Gorlin Syndrome-induced pluripotent stem cells are resistant against UV radiation.
ジャーナル Med Mol Morphol
Abstract Gorlin syndrome (GS) is an autosomal dominant genetic disorder involving Patched 1 (PTCH1) mutations. The PTCH1 is a receptor as well as an inhibitor of hedgehog (Hh) to sequester downstream Hh pathway molecules called Smoothened (SMO). PTCH1 mutations causes a variety of GS conditions including falx calcification, odontogenic keratocytes and basal cell carcinomas (BCC). Because PTCH1 is a major driver gene of sporadic BCC, GS patients are characteristically prone to BCC. In order to elucidate the pathological mechanism of BCC-prone GS patients, we investigated keratinocytes derived from GS patient specific iPS cells (G-OFiPSCs) which were generated and reported previously. We found that keratinocytes derived from G-OFiPSCs (GKCs) have increased expression of Hh target molecules. GKCs were irradiated and those cells showed high resistance to UV induced apoptosis. BCL2, known as anti-apoptotic molecule as well as Hh target, significantly increased in GKCs. Several molecules involved in DNA repair, cell cycle control, senescence, and genotoxic stress such as TP53, BRCA1 and GADD45A increased only in GKCs. GKCs are indicated to be resistant to UV irradiation by upregulating molecules which control DNA repair and genotoxic even under DNA damage caused by UV. The anti-apoptotic properties of GKCs may contribute BCC.
巻・号 54(2)
ページ 69-78
公開日 2021-6-1
DOI 10.1007/s00795-020-00264-4
PII 10.1007/s00795-020-00264-4
PMID 32816116
MeSH Apoptosis Asian People BRCA1 Protein / genetics BRCA1 Protein / metabolism Basal Cell Nevus Syndrome / genetics Basal Cell Nevus Syndrome / metabolism* Basal Cell Nevus Syndrome / physiopathology Carcinoma, Basal Cell Cell Cycle* Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism DNA Repair* Gene Expression Regulation Hedgehog Proteins / metabolism Humans Induced Pluripotent Stem Cells Keratinocytes / metabolism* Keratinocytes / physiology Keratinocytes / radiation effects Mutation Patched-1 Receptor / genetics* Signal Transduction Smoothened Receptor / genetics Tumor Suppressor Protein p53 / genetics Tumor Suppressor Protein p53 / metabolism Ultraviolet Rays*
IF 2.429
リソース情報
ヒト・動物細胞 Nips-B2(HPS0223)