PTEN Positively Regulates UVB-Induced DNA Damage Repair
| العنوان: | PTEN Positively Regulates UVB-Induced DNA Damage Repair |
|---|---|
| المؤلفون: | Carol S. Trempus, Mei Ming, Li Feng, Baozhong Zhao, Keyoumars Soltani, Weinong Han, Yu-Ying He, Christopher R. Shea, Robert C. Smart |
| المصدر: | Cancer Research. 71:5287-5295 |
| بيانات النشر: | American Association for Cancer Research (AACR), 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Keratinocytes, Cancer Research, Neoplasms, Radiation-Induced, Skin Neoplasms, Xeroderma pigmentosum, DNA Repair, Ultraviolet Rays, DNA damage, DNA repair, Down-Regulation, Human skin, Protein Serine-Threonine Kinases, medicine.disease_cause, p38 Mitogen-Activated Protein Kinases, Article, Cell Line, Mice, medicine, Animals, Humans, PTEN, CHEK1, RNA, Small Interfering, skin and connective tissue diseases, Papilloma, integumentary system, biology, PTEN Phosphohydrolase, medicine.disease, Molecular biology, DNA-Binding Proteins, Keratosis, Actinic, Checkpoint Kinase 2, Oncology, Checkpoint Kinase 1, Carcinoma, Squamous Cell, biology.protein, Cancer research, Skin cancer, Carcinogenesis, Precancerous Conditions, Protein Kinases, Proto-Oncogene Proteins c-akt, DNA Damage |
| الوصف: | Nonmelanoma skin cancer is the most common cancer in the United States, where DNA-damaging ultraviolet B (UVB) radiation from the sun remains the major environmental risk factor. However, the critical genetic targets of UVB radiation are undefined. Here we show that attenuating PTEN in epidermal keratinocytes is a predisposing factor for UVB-induced skin carcinogenesis in mice. In skin papilloma and squamous cell carcinoma (SCC), levels of PTEN were reduced compared with skin lacking these lesions. Likewise, there was a reduction in PTEN levels in human premalignant actinic keratosis and malignant SCCs, supporting a key role for PTEN in human skin cancer formation and progression. PTEN downregulation impaired the capacity of global genomic nucleotide excision repair (GG-NER), a critical mechanism for removing UVB-induced mutagenic DNA lesions. In contrast to the response to ionizing radiation, PTEN downregulation prolonged UVB-induced growth arrest and increased the activation of the Chk1 DNA damage pathway in an AKT-independent manner, likely due to reduced DNA repair. PTEN loss also suppressed expression of the key GG-NER protein xeroderma pigmentosum C (XPC) through the AKT/p38 signaling axis. Reconstitution of XPC levels in PTEN-inhibited cells restored GG-NER capacity. Taken together, our findings define PTEN as an essential genomic gatekeeper in the skin through its ability to positively regulate XPC-dependent GG-NER following DNA damage. Cancer Res; 71(15); 5287–95. ©2011 AACR. |
| تدمد: | 1538-7445 0008-5472 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::99587eed0113e8e47e22454496c25e63Test https://doi.org/10.1158/0008-5472.can-10-4614Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....99587eed0113e8e47e22454496c25e63 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15387445 00085472 |
|---|