Epigenetic gene silencing in cancer - a mechanism for early oncogenic pathway addiction?

被引:1294
作者
Baylin, SB [1 ]
Ohm, JE [1 ]
机构
[1] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA
关键词
D O I
10.1038/nrc1799
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Chromatin alterations have been associated with all stages of tumour formation and progression. The best characterized are epigenetically mediated transcriptional-silencing events that are associated with increases in DNA methylation - particularly at promoter regions of genes that regulate important cell functions. Recent evidence indicates that epigenetic changes might 'addict' cancer cells to altered signal-transduction pathways during the early stages of tumour development. Dependence on these pathways for cell proliferation or survival allows them to acquire genetic mutations in the same pathways, providing the cell with selective advantages that promote tumour progression. Strategies to reverse epigenetic gene silencing might therefore be useful in cancer prevention and therapy.
引用
收藏
页码:107 / 116
页数:10
相关论文
共 123 条
[1]   CLUES TO THE PATHOGENESIS OF FAMILIAL COLORECTAL-CANCER [J].
AALTONEN, LA ;
PELTOMAKI, P ;
LEACH, FS ;
SISTONEN, P ;
PYLKKANEN, L ;
MECKLIN, JP ;
JARVINEN, H ;
POWELL, SM ;
JEN, J ;
HAMILTON, SR ;
PETERSEN, GM ;
KINZLER, KW ;
VOGELSTEIN, B ;
DELACHAPELLE, A .
SCIENCE, 1993, 260 (5109) :812-816
[2]   Molecular detection of tumor cells in bronchoalveolar lavage fluid from patients with early stage lung cancer [J].
Ahrendt, SA ;
Chow, JT ;
Xu, LH ;
Yang, SC ;
Eisenberger, CF ;
Esteller, M ;
Herman, JG ;
Wu, L ;
Decker, PA ;
Jen, J ;
Sidransky, D .
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1999, 91 (04) :332-339
[3]  
Akama TO, 1997, CANCER RES, V57, P3294
[4]   GATA-4 and GATA-5 transcription factor genes and potential downstream antitumor target genes are epigenetically silenced in colorectal and gastric cancer [J].
Akiyama, Y ;
Watkins, N ;
Suzuki, H ;
Jair, KW ;
van Engeland, M ;
Esteller, M ;
Sakai, H ;
Ren, CY ;
Yuasa, Y ;
Herman, JG ;
Baylin, SB .
MOLECULAR AND CELLULAR BIOLOGY, 2003, 23 (23) :8429-8439
[5]   Gastroprotective peptide trefoil factor family 2 gene is activated by upstream stimulating factor but not by c-Myc in gastrointestinal cancer cells [J].
Al-azzeh, E ;
Dittrich, O ;
Vervoorts, J ;
Blin, N ;
Gött, P ;
Lüscher, B .
GUT, 2002, 51 (05) :685-690
[6]   Regulated recruitment of HP1 to a euchromatic gene induces mitotically heritable, epigenetic gene silencing: a mammalian cell culture model of gene variegation [J].
Ayyanathan, K ;
Lechner, MS ;
Bell, P ;
Maul, GG ;
Schultz, DC ;
Yamada, Y ;
Tanaka, K ;
Torigoe, K ;
Rauscher, FJ .
GENES & DEVELOPMENT, 2003, 17 (15) :1855-1869
[7]   Histone modifications and silencing prior to DNA methylation of a tumor suppressor gene [J].
Bachman, KE ;
Park, BH ;
Rhee, I ;
Rajagopalan, H ;
Herman, JG ;
Baylin, SB ;
Kinzler, KW ;
Vogelstein, B .
CANCER CELL, 2003, 3 (01) :89-95
[8]  
Bachman KE, 1999, CANCER RES, V59, P798
[9]   Aberrant methylation of p16INK4a is an early event in lung cancer and a potential biomarker for early diagnosis [J].
Belinsky, SA ;
Nikula, KJ ;
Palmisano, WA ;
Michels, R ;
Saccomanno, G ;
Gabrielson, E ;
Baylin, SB ;
Herman, JG .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (20) :11891-11896
[10]   PHYSICAL MAPPING ACROSS THE FRAGILE-X - HYPERMETHYLATION AND CLINICAL EXPRESSION OF THE FRAGILE-X SYNDROME [J].
BELL, MV ;
HIRST, MC ;
NAKAHORI, Y ;
MACKINNON, RN ;
ROCHE, A ;
FLINT, TJ ;
JACOBS, PA ;
TOMMERUP, N ;
TRANEBJAERG, L ;
FROSTERISKENIUS, U ;
KERR, B ;
TURNER, G ;
LINDENBAUM, RH ;
WINTER, R ;
PEMBREY, M ;
THIBODEAU, S ;
DAVIES, KE .
CELL, 1991, 64 (04) :861-866