A role of PDGFRα in basal cell carcinoma proliferation
| العنوان: | A role of PDGFRα in basal cell carcinoma proliferation |
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| المؤلفون: | Christopher B. Zachary, Xiaoli Zhang, Jeannette M. Bonifas, Ervin H. Epstein, Michelle Aszterbaum, Frank McCormick, Jingwu Xie |
| المصدر: | Proceedings of the National Academy of Sciences. 98:9255-9259 |
| بيانات النشر: | Proceedings of the National Academy of Sciences, 2001. |
| سنة النشر: | 2001 |
| مصطلحات موضوعية: | Patched, Skin Neoplasms, medicine.disease_cause, Cell Line, Mice, Growth factor receptor, GLI1, medicine, Animals, Humans, Hedgehog Proteins, Receptors, Platelet-Derived Growth Factor, Mutation, Multidisciplinary, integumentary system, biology, Cell growth, Proteins, Biological Sciences, Hedgehog signaling pathway, Cell biology, Carcinoma, Basal Cell, Cell culture, Trans-Activators, biology.protein, Mitogen-Activated Protein Kinases, Smoothened, Cell Division |
| الوصف: | Activation of the hedgehog pathway, through the loss of patched (PTC) or the activation of smoothened (SMO), occurs frequently in basal cell carcinoma (BCC), the most common human cancer. However, the molecular basis of this neoplastic effect is not understood. The downstream molecule Gli1 is known to mediate the biological effect of the pathway and is itself up-regulated in all BCCs. Gli1 can drive the production of BCCs in the mouse when overexpressed in the epidermis. Here we show that Gli1 can activate platelet-derived growth factor receptor α (PDGFRα) in C3H10T½ cells. Functional up-regulation of PDGFRα by Gli1 is accompanied by activation of the ras-ERK pathway, a pathway associated with cell proliferation. The relevance of this mechanismin vivois supported by a high level expression of PDGFRα in BCCs of mice and humans. In the murine BCC cell line ASZ001, in which both copies of the PTC gene are inactivated, DNA synthesis and cell proliferation can be slowed by re-expression of PTC, which down-regulates PDGFRα expression, or by downstream inhibition of PDGFRα with neutralizing antibodies. Therefore, we conclude that increased expression of PDGFRα may be an important mechanism by which mutations in the hedgehog pathway cause BCCs. |
| تدمد: | 1091-6490 0027-8424 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a1b01d804bd1aeee4bf9a5928cc90893 https://doi.org/10.1073/pnas.151173398 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....a1b01d804bd1aeee4bf9a5928cc90893 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10916490 00278424 |
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