التفاصيل البيبلوغرافية
| العنوان: |
Tumor suppressive function of E2F-1 on PTEN-induced serrated colorectal carcinogenesis |
| المؤلفون: |
Ana Velasco, Marta Vaquero, Cristina Megino, Sonia Gatius, Isidre Felip, Raúl Navaridas, Cristina Mirantes, Xavier Dolcet, Maria Alba Dosil, Carla Barceló, Izaskun Urdanibia, Anna Macià, Jordi Tarragona, Maria Santacana, Xavier Matias-Guiu, Carme Piñol, Nuria Eritja, Mónica Domingo, Oscar Maiques |
| المصدر: |
The Journal of Pathology. 247:72-85 |
| بيانات النشر: |
Wiley, 2018. |
| سنة النشر: |
2018 |
| مصطلحات موضوعية: |
0301 basic medicine, biology, Colorectal cancer, Context (language use), medicine.disease_cause, medicine.disease, Pathology and Forensic Medicine, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Downregulation and upregulation, 030220 oncology & carcinogenesis, Knockout mouse, medicine, Cancer research, biology.protein, Tensin, PTEN, E2F, Carcinogenesis |
| الوصف: |
Many human cancers present Phosphatase and tensin homolog (PTEN) deficiency and between 20 and 30% of colorectal tumors show PTEN loss. The transcription factor, E2 promoter binding factor 1 (E2F-1), exhibits tumor promoter or suppressive functions depending on cellular type and tissue context, but its role in the progression and development of colorectal carcinogenesis was largely unknown. Here, using a tamoxifen-inducible PTEN knockout mouse model, we have demonstrated that loss of PTEN leads to the development of colorectal tumorigenesis through the serrated pathway. Next, we studied PTEN loss-driven colorectal lesions in the context of E2F-1 deficiency in vivo. Our results revealed that monoallelic and biallelic absence of E2F-1 led to an increased incidence and progression of serrated tumorigenesis induced by PTEN loss. Finally, we investigated the mechanisms by which double PTEN/E2F-1 deficiency leads to enhanced tumorigenesis. We found that colorectal tumors from PTEN/E2F-1 double knockout mice and the human colorectal carcinoma cell line HT29 with shRNA-mediated downregulation of PTEN and E2F-1 exhibit hyperactivation of the RAS-MAPK pathway, accumulation of DNA damage and resistance to apoptosis. To date, this is the first preclinical study evaluating the effect of genetic deletion of E2F-1 in colorectal malignancies driven by PTEN deficiency. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. |
| تدمد: |
0022-3417 |
| DOI: |
10.1002/path.5168 |
| URL الوصول: |
https://explore.openaire.eu/search/publication?articleId=doi_________::0dfd08d71f8ec5a26ed0e8baeb0058b8
https://doi.org/10.1002/path.5168 |
| Rights: |
CLOSED |
| رقم الانضمام: |
edsair.doi...........0dfd08d71f8ec5a26ed0e8baeb0058b8 |
| قاعدة البيانات: |
OpenAIRE |