التفاصيل البيبلوغرافية
| العنوان: |
Sox7 is an independent checkpoint for β-Catenin function in prostate and colon epithelial cells |
| المؤلفون: |
Zhou, Wei, Dong, Jin-Tang, Varma, Vijay, Moreno, Carlos S, Vertino, Paula M, Yang, Vincent W, Sun, Xiaodong, Dong, Xue-Yuan, Liu, Xiuju, Lau, Stephen, Zhong, Diansheng, Guo, Lizheng |
| سنة النشر: |
2008 |
| المجموعة: |
University of Nairobi Digital Repository |
| مصطلحات موضوعية: |
β-catenin, colorectal cancer, prostate cancer, Sox7, chromosome 8p, tumor suppressor, promoter methylation, WNT signaling |
| الوصف: |
The presence of somatic β-catenin mutations in some prostate cancers implies that aberrant WNT signaling is involved in the cancer development. Although β-catenin stability is regulated by a multicomponent destruction complex, mutational alterations of β-catenin or other components of the destruction complexes are rare in prostate tumors. Therefore, β-catenin may be regulated by another protein in the prostate. In fact, recent linkage and somatic deletion analyses in prostate cancers reveal a 1.4-Mb candidate tumor suppressor locus on 8p23.1, which includes the Sox7 gene. Here we show that Sox7 protein expression was indeed down-regulated in 47% (15 of 32) of prostate adenocarcinomas. In addition, Sox7 mRNA was down-regulated in 60% of snap-frozen tumors. This down-regulation was found to be due to tumor-specific promoter hypermethylation, which was present in 48% (10 of 21) of primary prostate tumors and 44% (11 of 25) of prostate cancer cell lines/xenografts. We discovered that Sox7 protein physically interacts with β-catenin and suppresses β-catenin–mediated transcription by depleting active β-catenin. Furthermore, in HCT116 colorectal cancer cell lines with Sox7 inactivation, ectopic Sox7 expression suppressed cell proliferation and inhibited transcription that was activated by an endogenous mutant β-catenin. Although nearly all colorectal cancers contain mutations in β-catenin or adenomatous polyposis coli/axin, epigenetic silencing of Sox7 was still observed. These data suggest that Sox7 is a tumor suppressor that functions as an independent checkpoint for β-catenin transcriptional activity. Inactivation of Sox7 could promote the development of a majority of colorectal tumors and approximately half of prostate tumors. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| العلاقة: |
http://hdl.handle.net/11295/36518Test |
| الإتاحة: |
http://hdl.handle.net/11295/36518Test |
| رقم الانضمام: |
edsbas.12D904AF |
| قاعدة البيانات: |
BASE |
