| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Regular Articles |
Departments of 1 Pathology, 2 Hematopathology, 3 Molecular Therapeutics, and 4 Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas; 5 Department of Obstetrics and Gynecology, Research Division, University of British Columbia, Vancouver, British Columbia, Canada; and 6 Department of Medical Oncology, Dana-Farber Cancer Institute and Department of Medicine, Harvard Medical School, Boston, Massachusetts
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 or 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)-1ß, IL-6, and IL-8, that are up-regulated by the nuclear factor-
B pathway, which is known to contribute to the tumor growth of naturally ovarian cancer cells. Incubation with antibodies to IL-1ß 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-B-mediated cytokine activation. These cells provide a novel model system to study human ovarian cancer.
This article has been cited by other articles:
|
|
 |
|
  M. A. Edson, A. K. Nagaraja, and M. M. Matzuk The Mammalian Ovary from Genesis to Revelation Endocr. Rev., October 1, 2009; 30(6): 624 - 712. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W.-X. Ding, H.-M. Ni, W. Gao, X. Chen, J. H. Kang, D. B. Stolz, J. Liu, and X.-M. Yin Oncogenic transformation confers a selective susceptibility to the combined suppression of the proteasome and autophagy Mol. Cancer Ther., July 1, 2009; 8(7): 2036 - 2045. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Wei, W. Guo, S. Wu, L. Wang, Y. Lu, B. Xu, J. Liu, and B. Fang Inhibiting JNK Dephosphorylation and Induction of Apoptosis by Novel Anticancer Agent NSC-741909 in Cancer Cells J. Biol. Chem., June 19, 2009; 284(25): 16948 - 16955. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. V. Levina, B. Nolen, Y. Su, A. K. Godwin, D. Fishman, J. Liu, G. Mor, L. G. Maxwell, R. B. Herberman, M. J. Szczepanski, et al. Biological Significance of Prolactin in Gynecologic Cancers Cancer Res., June 15, 2009; 69(12): 5226 - 5233. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Sasaki, M. Narisawa-Saito, T. Yugawa, M. Fujita, H. Tashiro, H. Katabuchi, and T. Kiyono Oncogenic transformation of human ovarian surface epithelial cells with defined cellular oncogenes Carcinogenesis, March 1, 2009; 30(3): 423 - 431. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L.-F. Dong, R. Freeman, J. Liu, R. Zobalova, A. Marin-Hernandez, M. Stantic, J. Rohlena, K. Valis, S. Rodriguez-Enriquez, B. Butcher, et al. Suppression of Tumor Growth In vivo by the Mitocan {alpha}-tocopheryl Succinate Requires Respiratory Complex II Clin. Cancer Res., March 1, 2009; 15(5): 1593 - 1600. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Hakim, C. P. Barry, H. J. Barnes, K. E. Anderson, J. Petitte, R. Whitaker, J. M. Lancaster, R. M. Wenham, D. K. Carver, J. Turbov, et al. Ovarian Adenocarcinomas in the Laying Hen and Women Share Similar Alterations in p53, ras, and HER-2/neu Cancer Prevention Research, February 1, 2009; 2(2): 114 - 121. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Guo, S. Wu, J. Liu, and B. Fang Identification of a Small Molecule with Synthetic Lethality for K-Ras and Protein Kinase C Iota Cancer Res., September 15, 2008; 68(18): 7403 - 7408. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Wang, A. M. Urvalek, J. Liu, and J. Zhao Activation of KLF8 Transcription by Focal Adhesion Kinase in Human Ovarian Epithelial and Cancer Cells J. Biol. Chem., May 16, 2008; 283(20): 13934 - 13942. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Mahale, Z. A.T. Khan, M. Igarashi, G. J. Nanjangud, R. F. Qiao, S. Yao, S. W. Lee, and S. A. Aaronson Clonal Selection in Malignant Transformation of Human Fibroblasts Transduced with Defined Cellular Oncogenes Cancer Res., March 1, 2008; 68(5): 1417 - 1426. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Zecchini, M. Bianchi, N. Colombo, R. Fasani, G. Goisis, C. Casadio, G. Viale, J. Liu, M. Herlyn, A. K. Godwin, et al. The Differential Role of L1 in Ovarian Carcinoma and Normal Ovarian Surface Epithelium Cancer Res., February 15, 2008; 68(4): 1110 - 1118. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. B. Ancrile, K. M. O'Hayer, and C. M. Counter Oncogenic Ras-Induced Expression of Cytokines: A New Target of Anti-Cancer Therapeutics Mol. Interv., February 1, 2008; 8(1): 22 - 27. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Huynh, C. C. M. Teo, and K. C. Soo Bevacizumab and rapamycin inhibit tumor growth in peritoneal model of human ovarian cancer Mol. Cancer Ther., November 1, 2007; 6(11): 2959 - 2966. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M El-Naggar, M. T Malik, A. Martin, J. P Moore, M. Proctor, T. Hamid, and S. S Kakar Development of cystic glandular hyperplasia of the endometrium in Mullerian inhibitory substance type II receptor-pituitary tumor transforming gene transgenic mice J. Endocrinol., July 1, 2007; 194(1): 179 - 191. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. W. Young, F. C. Mei, D. G. Rosen, G. Yang, N. Li, J. Liu, and X. Cheng Up-regulation of Tumor Susceptibility Gene 101 Protein in Ovarian Carcinomas Revealed by Proteomics Analyses Mol. Cell. Proteomics, February 1, 2007; 6(2): 294 - 304. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Yang, D. G. Rosen, I. Mercado-Uribe, J. A. Colacino, G. B. Mills, R. C. Bast Jr, C. Zhou, and J. Liu Knockdown of p53 combined with expression of the catalytic subunit of telomerase is sufficient to immortalize primary human ovarian surface epithelial cells Carcinogenesis, January 1, 2007; 28(1): 174 - 182. [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]
|
|
|
|
|
|
F. Teraishi, W. Guo, L. Zhang, F. Dong, J. J. Davis, T. Sasazuki, S. Shirasawa, J. Liu, and B. Fang Activation of Sterile20-Like Kinase 1 in Proteasome Inhibitor Bortezomib-Induced Apoptosis in Oncogenic K-ras-Transformed Cells. Cancer Res., June 15, 2006; 66(12): 6072 - 6079. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Hossein Pourgholami, Z. Yan Cai, Y. Lu, L. Wang, and D. Lawson Morris Albendazole: a Potent Inhibitor of Vascular Endothelial Growth Factor and Malignant Ascites Formation in OVCAR-3 Tumor-Bearing Nude Mice. Clin. Cancer Res., March 15, 2006; 12(6): 1928 - 1935. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Matsumura, M. Mandai, M. Miyanishi, K. Fukuhara, T. Baba, T. Higuchi, M. Kariya, K. Takakura, and S. Fujii Oncogenic Property of Acrogranin in Human Uterine Leiomyosarcoma: Direct Evidence of Genetic Contribution in In vivo Tumorigenesis Clin. Cancer Res., March 1, 2006; 12(5): 1402 - 1411. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Hu, D. G. Rosen, Y. Zhou, L. Feng, G. Yang, J. Liu, and P. Huang Mitochondrial Manganese-Superoxide Dismutase Expression in Ovarian Cancer: ROLE IN CELL PROLIFERATION AND RESPONSE TO OXIDATIVE STRESS J. Biol. Chem., November 25, 2005; 280(47): 39485 - 39492. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Okamoto, T. Nikaido, K. Ochiai, S. Takakura, M. Saito, Y. Aoki, N. Ishii, N. Yanaihara, K. Yamada, O. Takikawa, et al. Indoleamine 2,3-Dioxygenase Serves as a Marker of Poor Prognosis in Gene Expression Profiles of Serous Ovarian Cancer Cells Clin. Cancer Res., August 15, 2005; 11(16): 6030 - 6039. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Daikoku, D. Wang, S. Tranguch, J. D. Morrow, S. Orsulic, R. N. DuBois, and S. K. Dey Cyclooxygenase-1 Is a Potential Target for Prevention and Treatment of Ovarian Epithelial Cancer Cancer Res., May 1, 2005; 65(9): 3735 - 3744. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. W. Cheng, J. P. Lahad, J. W. Gray, and G. B. Mills Emerging Role of RAB GTPases in Cancer and Human Disease Cancer Res., April 1, 2005; 65(7): 2516 - 2519. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Spillman and A. Berchuck Stretching the Surface Epithelium Reproductive Sciences, December 1, 2004; 11(8): 501 - 502. [PDF]
|
|
|
|
|
|
T. W. Young, F. C. Mei, G. Yang, J. A. Thompson-Lanza, J. Liu, and X. Cheng Activation of Antioxidant Pathways in Ras-Mediated Oncogenic Transformation of Human Surface Ovarian Epithelial Cells Revealed by Functional Proteomics and Mass Spectrometry Cancer Res., July 1, 2004; 64(13): 4577 - 4584. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
