Emerging roles of Kruppel-like factor 6 and Kruppel-like factor 6 splice variant 1 in ovarian cancer progression and treatment.
Emerging roles of Kruppel-like factor 6 and Kruppel-like factor 6 splice variant 1 in ovarian cancer progression and treatment.
复制标题
DOI：
10.1002/msj.20150
复制
发表时间：
2009-12
影响因子：
--
通讯作者：
Martignetti, John A.
中科院分区：
文献类型：
--
作者：
DiFeo, Analisa;Narla, Goutham;Martignetti, John A.
关键词：
Epithelial ovarian cancer is one of the most lethal gynecologic cancers and the fifth most frequent cause of female cancer deaths in the United States. Despite dramatic treatment successes in other cancers through the use of molecular agents targeted against genetically defined events driving cancer development and progression, very few insights into epithelial ovarian cancer have been translated from the laboratory to the clinic. If advances are to be made in the early diagnosis, prevention, and treatment of this disease, it will be critical to characterize the common and private (personalized) genetic defects underlying the development and spread of epithelial ovarian cancer. The tumor suppressor Kruppel-like factor 6 and its alternatively spliced, oncogenic isoform, Kruppel-like factor 6 splice variant 1, are members of the Kruppel-like zinc finger transcription factor family of proteins, which have diverse roles in cellular differentiation, development, proliferation, growth-related signal transduction, and apoptosis. Inactivation of Kruppel-like factor 6 and overexpression of Kruppel-like factor 6 splice variant 1 have been associated with the progression of a number of human cancers and even with patient survival. This article summarizes our recent findings demonstrating that a majority of epithelial ovarian cancer tumors have Kruppel-like factor 6 allelic loss and decreased expression coupled with increased expression of Kruppel-like factor 6 splice variant 1. The targeted reduction of Kruppel-like factor 6 in ovarian cancer cell lines results in marked increases in cell proliferation, invasion, tumor growth, angiogenesis, and intraperitoneal dissemination in vivo. In contrast, the inhibition of Kruppel-like factor 6 splice variant 1 decreases cellular proliferation, invasion, angiogenesis, and tumorigenicity; this provides the rationale for its potential therapeutic application. These results and our recent demonstration that the inhibition of Kruppel-like factor 6 splice variant 1 can dramatically prolong survival in a preclinical mouse model of ovarian cancer are reviewed and discussed.
登录
查看更多内容
DOI：
10.1093/jnci/94.18.1365
发表时间：
2002-09-18
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
Brose, MS;Rebbeck, TR;Weber, BL
通讯作者：
Weber, BL
影响因子：
8
作者：
Cho, YG;Kim, CJ;Park, WS
通讯作者：
Park, WS
影响因子：
11.2
作者：
DiFeo, Analisa;Huang, Fei;Martignetti, John A.
通讯作者：
Martignetti, John A.
影响因子：
6.4
作者：
Camacho-Vanegas, Olga;Narla, Goutham;Martignetti, John A.
通讯作者：
Martignetti, John A.
影响因子：
64.8
作者：
Elbashir, SM;Harborth, J;Tuschl, T
通讯作者：
Tuschl, T