Expression of the ZEB1 (δEF1) transcription factor in human: additional insights

被引:49
作者
Hurt, Elaine M. [2 ]
Saykally, Jessica N. [1 ]
Anose, Bynthia M. [3 ]
Kalli, Kimberly R. [4 ]
Sanders, Michel M. [1 ]
机构
[1] Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN 55455 USA
[2] NCI, Canc Stem Cell Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Frederick, MD 21702 USA
[3] Bethel Univ, Dept Chem, St Paul, MN 55112 USA
[4] Mayo Clin, Coll Med, Dept Oncol, Rochester, MN 55905 USA
关键词
ZEB1; delta EF1; Estrogen; Gynecologic carcinomas; TCF8;
D O I
10.1007/s11010-008-9860-z
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The zinc finger E-box binding transcription factor ZEB1 (delta EF1/Nil-2-a/AREB6/zfhx1a/TCF8/zfhep/BZP) is emerging as an important regulator of the epithelial to mesenchymal transitions (EMT) required for development and cancer metastasis. ZEB1 promotes EMT by repressing genes contributing to the epithelial phenotype while activating those associated with the mesenchymal phenotype. TCF8 (zfhx1a), the gene encoding ZEB1, is induced by several potentially oncogenic ligands including TGF-beta, estrogen, and progesterone. TGF-beta appears to activate EMT, at least in part, by inducing ZEB1. However, our understanding of how ZEB1 contributes to signaling pathways elicited by estrogen and progesterone is quite limited, as is our understanding of its functional roles in normal adult tissues. To begin to address these questions, a human tissue mRNA array analysis was done. In adults, the highest ZEB1 mRNA expression is in bladder and uterus, whereas in the fetus highest expression is in lung, thymus, and heart. To further investigate the regulation of TCF8 by estrogen, ZEB1 mRNA was measured in ten estrogen-responsive cell lines, but it is only induced in the OV266 ovarian carcinoma line. Although high expression of ZEB1 mRNA is estrogen-dependent in normal human ovarian and endometrial biopsies, high expression is estrogen-independent in late stage ovarian and endometrial carcinomas, raising the possibility that deregulated expression promotes cancer progression. In contrast, TCF8 is at least partially deleted in 4 of 5 well-differentiated, grade I endometrial carcinomas, which may contribute to their non-aggressive phenotype. These data support the contention that high ZEB1 encourages gynecologic carcinoma progression.
引用
收藏
页码:89 / 99
页数:11
相关论文
共 54 条
[1]  
Abal M, 2006, HISTOL HISTOPATHOL, V21, P197, DOI 10.14670/HH-21.197
[2]   The transcription factor ZEB1 (δEF1) promotes tumour cell dedifferentiation by repressing master regulators of epithelial polarity [J].
Aigner, K. ;
Dampier, B. ;
Descovich, L. ;
Mikula, M. ;
Sultan, A. ;
Schreiber, M. ;
Mikulits, W. ;
Brabletz, T. ;
Strand, D. ;
Obrist, P. ;
Sommergruber, W. ;
Schweifer, N. ;
Wernitznig, A. ;
Beug, H. ;
Foisner, R. ;
Eger, A. .
ONCOGENE, 2007, 26 (49) :6979-6988
[3]  
Baldwin WS, 1998, IN VITRO CELL DEV-AN, V34, P649
[4]   Frequent loss of heterozygosity on chromosome 10q in muscle-invasive transitional cell carcinomas of the bladder [J].
Cappellen, D ;
deMedina, SGD ;
Chopin, D ;
Thiery, JP ;
Radvanyi, F .
ONCOGENE, 1997, 14 (25) :3059-3066
[5]   Immortalization of human uterine leiomyoma and myometrial cell lines after induction of telomerase activity: Molecular and phenotypic characteristics [J].
Carney, SA ;
Tahara, H ;
Swartz, CD ;
Risinger, JI ;
He, H ;
Moore, AB ;
Haseman, JK ;
Barrett, JC ;
Dixon, D .
LABORATORY INVESTIGATION, 2002, 82 (06) :719-728
[6]  
Chamberlain EM, 1999, MOL CELL BIOL, V19, P3600
[7]   NF-κB represses E-cadherin expression and enhances epithelial to mesenchymal transition of mammary epithelial cells:: potential involvement of ZEB-1 and ZEB-2 [J].
Chua, H. L. ;
Bhat-Nakshatri, P. ;
Clare, S. E. ;
Morimiya, A. ;
Badve, S. ;
Nakshatri, H. .
ONCOGENE, 2007, 26 (05) :711-724
[8]   Biological characterization of human epithelial ovarian carcinoma cells in primary culture: The insulin-like growth factor system [J].
Conover, CA ;
Hartmann, LC ;
Bradley, S ;
Stalboerger, P ;
Klee, GC ;
Kalli, KR ;
Jenkins, RB .
EXPERIMENTAL CELL RESEARCH, 1998, 238 (02) :439-449
[9]  
Darling DS, 1998, MOL CELL ENDOCRINOL, V139, P25
[10]   Cyclooxygenase-2-dependent regulation of E-cadherin:: Prostaglandin E2 induces transcriptional repressors ZEB1 and snail in non-small cell lung cancer [J].
Dohadwala, Mariam ;
Yang, Seok-Chul ;
Luo, Jie ;
Sharma, Sherven ;
Batra, Raj K. ;
Huang, Min ;
Lin, Ying ;
Goodglick, Lee ;
Krysan, Kostyantyn ;
Fishbein, Michael C. ;
Hong, Longsheng ;
Lai, Chi ;
Cameron, Robert B. ;
Gemmill, Robert M. ;
Drabkin, Harry A. ;
Dubinett, Steven M. .
CANCER RESEARCH, 2006, 66 (10) :5338-5345