A Genetically Defined Model for Human Ovarian Cancer

Jinsong Liu, Gong Yang, Jennifer A. Thompson-Lanza, Armand Glassman, Kimberly Hayes, Andrea Patterson, Rebecca T. Marquez, Nelly Auersperg, Yinhua Yu, William C. Hahn, Gordon Mills, Robert C. Bast

Research output: Contribution to journalArticle

220 Citations (Scopus)

Abstract

Disruptions of the p53, retinoblastoma (Rb), and RAS signaling pathways and activation of human telomerase reverse transcriptase (hTERT) are common in human ovarian cancer; however, their precise role in ovarian cancer development is not clear. We thus introduced the catalytic subunit of hTERT, the SV40 early genomic region, and the oncogenic alleles of human HRAS or KRAS into human ovarian surface epithelial cells and examined the phenotype and gene expression profile of those cells. Disruption of p53 and Rb pathway by SV40 early genomic region and hTERT immortalized but did not transform the cells. Introduction of HRASV12 of KRASV12 into the immortalized cells, however, allowed them to form s.c. tumors after injection into immunocompromised mice. Peritoneal injection of the transformed cells produced undifferentiated carcinoma or malignant mixed Mullerian tumor and developed ascites; the tumor cells are focally positive for CA125 and mesothelin. Gene expression profile analysis of transformed cells revealed elevated expression of several cytokines, including interleukin (IL)-1β, IL-6, and IL-8, that are up-regulated by the nuclear factor-κB pathway, which is known to contribute to the tumor growth of naturally ovarian cancer cells. Incubation with antibodies to IL-1β or IL-8 led to apoptosis in the ras-transformed cells and ovarian cancer cells but not in immortalized cells that had not been transformed. Thus, the transformed human ovarian surface epithelial cells recapitulated many features of natural ovarian cancer including a subtype of ovarian cancer histology, formation of ascites, CA125 expression, and nuclear factor-κB-mediated cytokine activation. These cells provide a novel model system to study human ovarian cancer.

Original languageEnglish (US)
Pages (from-to)1655-1663
Number of pages9
JournalCancer Research
Volume64
Issue number5
DOIs
StatePublished - Mar 1 2004
Externally publishedYes

Fingerprint

Ovarian Neoplasms
Retinoblastoma
Interleukin-8
Interleukin-1
Transcriptome
Ascites
Epithelial Cells
Malignant Mixed Tumor
Cytokines
Neoplasms
Injections
Interleukin-6
Catalytic Domain
Histology
Alleles
Apoptosis
Carcinoma
Phenotype
Antibodies

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Liu, J., Yang, G., Thompson-Lanza, J. A., Glassman, A., Hayes, K., Patterson, A., ... Bast, R. C. (2004). A Genetically Defined Model for Human Ovarian Cancer. Cancer Research, 64(5), 1655-1663. https://doi.org/10.1158/0008-5472.CAN-03-3380

A Genetically Defined Model for Human Ovarian Cancer. / Liu, Jinsong; Yang, Gong; Thompson-Lanza, Jennifer A.; Glassman, Armand; Hayes, Kimberly; Patterson, Andrea; Marquez, Rebecca T.; Auersperg, Nelly; Yu, Yinhua; Hahn, William C.; Mills, Gordon; Bast, Robert C.

In: Cancer Research, Vol. 64, No. 5, 01.03.2004, p. 1655-1663.

Research output: Contribution to journalArticle

Liu, J, Yang, G, Thompson-Lanza, JA, Glassman, A, Hayes, K, Patterson, A, Marquez, RT, Auersperg, N, Yu, Y, Hahn, WC, Mills, G & Bast, RC 2004, 'A Genetically Defined Model for Human Ovarian Cancer', Cancer Research, vol. 64, no. 5, pp. 1655-1663. https://doi.org/10.1158/0008-5472.CAN-03-3380
Liu J, Yang G, Thompson-Lanza JA, Glassman A, Hayes K, Patterson A et al. A Genetically Defined Model for Human Ovarian Cancer. Cancer Research. 2004 Mar 1;64(5):1655-1663. https://doi.org/10.1158/0008-5472.CAN-03-3380
Liu, Jinsong ; Yang, Gong ; Thompson-Lanza, Jennifer A. ; Glassman, Armand ; Hayes, Kimberly ; Patterson, Andrea ; Marquez, Rebecca T. ; Auersperg, Nelly ; Yu, Yinhua ; Hahn, William C. ; Mills, Gordon ; Bast, Robert C. / A Genetically Defined Model for Human Ovarian Cancer. In: Cancer Research. 2004 ; Vol. 64, No. 5. pp. 1655-1663.
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