Molecular changes associated with oral dysplasia progression and acquisition of immortality: potential for its reversal by 5-azacytidine.
Molecular changes associated with oral dysplasia progression and acquisition of immortality: potential for its reversal by 5-azacytidine.
复制标题
与口腔发育不良进展和获得永生相关的分子变化：5-氮杂胞苷逆转其的潜力。
作者：
F. McGregor;A. Muntoni;J. Fleming;Judith Brown;D. Felix;D. Macdonald;E. Parkinson;P. Harrison
This study has identified molecular changes characteristic of early oral cancer progression. We reported previously that acquisition of the immortal phenotype is an early event in oral cancer development (F. McGregor et al., Cancer Res., 57: 3886-3889, 1997); our current data indicate that about half of oral dysplasia cultures are immortal, and this is associated with loss of expression of retinoic acid receptor (RAR)-beta and the cell cycle inhibitor p16(ink4a) (p16), p53 mutations, and increased levels of telomerase/human telomerase reverse transcriptase mRNA. In contrast, increased expression of the epidermal growth factor receptor, known to be a characteristic of oral cancer, does not occur until after the dysplasia stage in squamous cell carcinomas. Acquisition of invasive properties as judged by an in vitro Matrigel invasion assay also does not occur until the carcinoma stage and is further increased in metastases. Interestingly, one atypical mortal dysplasia with a considerably extended life span has lost expression of RAR-beta and p16, but it still expresses only wild-type p53 (albeit at a higher level than normal) and has not activated telomerase. RAR-beta and/or p16 re-expression can be induced by treatment with 5-aza-2-deoxycytidine (Aza-C) in some immortal dysplasias, and this has been shown to be due to silencing of gene expression by promoter methylation. Aza-C treatment also down-regulated telomerase activity and human telomerase reverse transcriptase mRNA. Interestingly, with one dysplasia, Aza-C was able to reverse its immortal phenotype, as judged by morphological criteria and expression of the senescence-associated acid beta-galactosidase activity during terminal growth arrest; this immortal dysplasia was the only one in which Aza-C treatment not only down-regulated telomerase activity but also induced re-expression of both RAR-beta and p16. The possibility of reversing the immortal phenotype of some dysplasias by Aza-C may be of clinical usefulness.
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影响因子：
11.2
作者：
X. C. Xu;Jae Y. Ro;J. S. Lee;Dong M. Shin;W. Hong;R. Lotan
通讯作者：
X. C. Xu;Jae Y. Ro;J. S. Lee;Dong M. Shin;W. Hong;R. Lotan
DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
DIMRI, GP;LEE, XH;CAMPISI, J
通讯作者：
CAMPISI, J
细胞周期蛋白 D1 和 E 的过度表达在支气管癌前病变中很常见，并且先于鳞状细胞癌的发展。
DOI：
--
发表时间：
1999
期刊：
Cancer research.
影响因子：
--
作者：
Lonardo,F;Rusch,V;Langenfeld,J;Dmitrovsky,E;Klimstra,DS
通讯作者：
Klimstra,DS
口腔正常上皮和发育异常白斑中细胞增殖的标志物。
DOI：
--
发表时间：
1998
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.
影响因子：
--
作者：
Liu,SC;Sauter,ER;Clapper,ML;Feldman,RS;Levin,L;Chen,SY;Yen,TJ;Ross,E;Engstrom,PF;Klein-Szanto,AJ
通讯作者：
Klein-Szanto,AJ
DOI：
--
发表时间：
1998
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
J. Rubin Grandis;D. Tweardy;M. Melhem
通讯作者：
J. Rubin Grandis;D. Tweardy;M. Melhem