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Disruption of the retinoblastoma pathway by small interfering RNA and ectopic expression of the catalytic subunit of telomerase lead to immortalization of human ovarian surface epithelial cells

Oncogene volume 26, pages 1492–1498 (2007)Cite this article

A Correction to this article was published on 17 April 2020

Abstract

The risk of developing ovarian cancer is about 1% over a lifetime, but it is the most deadly gynecologic cancer, in part due to lack of diagnostic markers for early-stage disease and cell model system for studying early neoplastic changes. Most existing immortal human ovarian surface epithelial cells were achieved by using viral protein such as SV40 T/t antigen or E6/E7, which inactivate multiple cellular pathways. In the current study, we used a small interfering RNA (siRNA) against the retinoblastoma gene (pRb) and ectopic expression of human telomerase reverse transcriptase (hTERT) to immortalize the primary ovarian epithelial cell line OSE137 and two additional human ovarian surface epithelial cells. The immortalized OSE137 showed increased telomerase activity, lengthened telomeres, increased G2/M phase, altered cell-cycle regulatory proteins but nontumorigenic. As both Rb and hTERT pathways are commonly altered in human ovarian cancer and these genetic changes are faithfully modeled in these cells without using viral protein, these immortal cells represent an authentic in vitro model system with which to study the initiation and progression of human ovarian cancer.

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Abbreviations

hTERT:

human telomerase reverse transcriptase

pRb:

retinoblastoma protein

TRAP:

telomeric repeat amplification protocol

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Acknowledgements

This work was supported in part by a research scholar grant from the American Cancer Society (JL) and Cancer Center Core grant (CA016672) from the National Cancer Institute (MD Anderson Cancer Center). We thank Drs Sandy Chang and Asha Multani from the MD Anderson Molecular Cytogenetics Core Facility for karyotyping the immortalized cells.

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Authors and Affiliations

  1. Department of Pathology, The University of Texas MD Anderson Cancer Center, Holcombe Boulevard, Houston, TX, USA

    G Yang, D G Rosen, J A Colacino, I Mercado-Uribe & J Liu

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  1. G Yang
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  2. D G Rosen
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  3. J A Colacino
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  4. I Mercado-Uribe
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  5. J Liu
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Correspondence to J Liu.

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Yang, G., Rosen, D., Colacino, J. et al. Disruption of the retinoblastoma pathway by small interfering RNA and ectopic expression of the catalytic subunit of telomerase lead to immortalization of human ovarian surface epithelial cells. Oncogene 26, 1492–1498 (2007). https://doi.org/10.1038/sj.onc.1209905

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