Carcinogenesis Advance Access published online on July 8, 2006
Carcinogenesis, doi:10.1093/carcin/bgl115
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
* To whom correspondence should be addressed. Ovarian cancer is developed from a single layer of thin epithelial cells covering the surface of ovary, named human ovarian surface epithelial cells. Like all primary human cells, human ovarian surface epithelial cells have a finite life span and will go into senescence and eventually die when cultured in vitro. Immortalized human ovarian surface epithelial cells will provide an important model system with which to study ovarian cancer initiation and progression. Here, we show that silencing p53 expression with retrovirus-mediated small interfering RNA can delay the senescence and extend cell passage number, but is not sufficient to immortalize normal ovarian surface epithelial cells. Introduction of the catalytic subunit of telomerase is similarly insufficient to achieve immortalization. However, concurrent disruption of p53 expression with small interfering RNA retroviral constructs and ectopic expression of the catalytic subunit of telomerase was sufficient to induce cellular immortalization in 3 of 3 human ovarian surface epithelial cell cultures tested. The immortalzation is associated with increased telomerase activity and telomere length, and attenuated response of cell cycle regulatory proteins to irradiaiton. The resultant immortal cells continued to express the same specific cytokeratins 8 and 18 as parental cells did, indicating that the epithelial characters are still maintained in the immortal cells. In addition, the immortalized cells are nontumorigenic and nearly diploid, which is in constrast with one immortalized by SV40 T/t antigens and hTERT. As both p53 pathway dysfunction and activation of telomerase are commonly present in human ovarian cancer, these immortal cells provide an authetic cell model system for the study of the human ovarian cancer initiation, progression, differentiation, and chemoprevention.
Received February 15, 2006
Revised June 13, 2006
Accepted June 20, 2006
CARCINOGENESIS
Knockdown of p53 combined with expression of the catalytic subunit of telomerase is sufficient to immortalize primary human ovarian surface epithelial cells
Gong Yang 1,
Daniel G. Rosen 1,
Imelda Mercado-Uribe 1,
Justin A. Colacino 1,
Gordon B. Mills 2,
Robert C. Bast Jr 3,
Chenyi Zhou 1,
and
Jinsong Liu 1 *
2 Department of Molecular Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
3 Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
Jinsong Liu, E-mail: jliu{at}mdanderson.org
Abstract 
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  D. Wang, Z. Zhao, A. Caperell-Grant, G. Yang, S. C. Mok, J. Liu, R. M. Bigsby, and Y. Xu S1P differentially regulates migration of human ovarian cancer and human ovarian surface epithelial cells Mol. Cancer Ther., July 1, 2008; 7(7): 1993 - 2002. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. N. Landen Jr, M. J. Birrer, and A. K. Sood Early Events in the Pathogenesis of Epithelial Ovarian Cancer J. Clin. Oncol., February 20, 2008; 26(6): 995 - 1005. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Yang, D. G. Rosen, Z. Zhang, R. C. Bast Jr., G. B. Mills, J. A. Colacino, I. Mercado-Uribe, and J. Liu The chemokine growth-regulated oncogene 1 (Gro-1) links RAS signaling to the senescence of stromal fibroblasts and ovarian tumorigenesis PNAS, October 31, 2006; 103(44): 16472 - 16477. [Abstract] [Full Text] [PDF]
|
|