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J. Biol. Chem., Vol. 276, Issue 24, 20809-20812, June 15, 2001
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From the Elevated tumor cyclooxygenase (COX-2) expression
is associated with increased angiogenesis, tumor invasion, and
suppression of host immunity. We have previously shown that genetic
inhibition of tumor COX-2 expression reverses the immunosuppression
induced by non-small cell lung cancer (NSCLC). To assess the impact of COX-2 expression in lung cancer invasiveness, NSCLC cell lines were
transduced with a retroviral vector expressing the human COX-2 cDNA
in the sense (COX-2-S) and antisense (COX-2-AS) orientations. COX-2-S
clones expressed significantly more COX-2 protein, produced 10-fold
more prostaglandin E2, and demonstrated an
enhanced invasive capacity compared with control vector-transduced or
parental cells. CD44, the cell surface receptor for hyaluronate, was
overexpressed in COX-2-S cells, and specific blockade of CD44
significantly decreased tumor cell invasion. In contrast, COX-2-AS
clones had a very limited capacity for invasion and showed diminished
expression of CD44. These findings suggest that a COX-2-mediated,
CD44-dependent pathway is operative in NSCLC invasion.
Because tumor COX-2 expression appears to have a multifaceted role in
conferring the malignant phenotype, COX-2 may be an important target
for gene or pharmacologic therapy in NSCLC.
Lung Cancer Research Program of the UCLA Jonsson
Comprehensive Cancer Center and the Division of Pulmonary
and Critical Care Medicine, Departments of Medicine and
§ Radiation Oncology, UCLA, School of Medicine, and the
¶ Veterans Affairs Greater Los Angeles Healthcare System, Los
Angeles California 90095-1690
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J. T. Mao, M. D. Roth, K. J. Serio, F. Baratelli, L. Zhu, E. C. Holmes, R. M. Strieter, and S. M. Dubinett Celecoxib Modulates the Capacity for Prostaglandin E2 and Interleukin-10 Production in Alveolar Macrophages from Active Smokers Clin. Cancer Res., December 1, 2003; 9(16): 5835 - 5841. [Abstract] [Full Text] [PDF]
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M. S. De Lorenzo, K. Yamaguchi, K. Subbaramaiah, and A. J. Dannenberg Bryostatin-1 Stimulates the Transcription of Cyclooxygenase-2: Evidence for an Activator Protein-1-Dependent Mechanism Clin. Cancer Res., October 15, 2003; 9(13): 5036 - 5043. [Abstract] [Full Text] [PDF]
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S. Sharma, M. Stolina, S.-C. Yang, F. Baratelli, J. F. Lin, K. Atianzar, J. Luo, L. Zhu, Y. Lin, M. Huang, et al. Tumor Cyclooxygenase 2-dependent Suppression of Dendritic Cell Function Clin. Cancer Res., March 1, 2003; 9(3): 961 - 968. [Abstract] [Full Text] [PDF]
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N. Heuze-Vourc'h, L. Zhu, K. Krysan, R. K. Batra, S. Sharma, and S. M. Dubinett Abnormal Interleukin 10R{alpha} Expression Contributes to the Maintenance of Elevated Cyclooxygenase-2 in Non-Small Cell Lung Cancer Cells Cancer Res., February 15, 2003; 63(4): 766 - 770. [Abstract] [Full Text] [PDF]
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M. Dohadwala, R. K. Batra, J. Luo, Y. Lin, K. Krysan, M. Pold, S. Sharma, and S. M. Dubinett Autocrine/Paracrine Prostaglandin E2 Production by Non-small Cell Lung Cancer Cells Regulates Matrix Metalloproteinase-2 and CD44 in Cyclooxygenase-2-dependent Invasion J. Biol. Chem., December 20, 2002; 277(52): 50828 - 50833. [Abstract] [Full Text] [PDF]
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K.-i. Sunayama, H. Konno, T. Nakamura, H. Kashiwabara, T. Shoji, T. Tsuneyoshi, and S. Nakamura The role of cyclooxygenase-2 (COX-2) in two different morphological stages of intestinal polyps in APC{Delta}474 knockout mice Carcinogenesis, August 1, 2002; 23(8): 1351 - 1359. [Abstract] [Full Text] [PDF]
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K. Subbaramaiah, L. Norton, W. Gerald, and A. J. Dannenberg Cyclooxygenase-2 Is Overexpressed in HER-2/neu-positive Breast Cancer. EVIDENCE FOR INVOLVEMENT OF AP-1 AND PEA3 J. Biol. Chem., May 17, 2002; 277(21): 18649 - 18657. [Abstract] [Full Text] [PDF]
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K. Subbaramaiah, P. A. Cole, and A. J. Dannenberg Retinoids and Carnosol Suppress Cyclooxygenase-2 Transcription by CREB-binding Protein/p300-dependent and -independent Mechanisms Cancer Res., May 1, 2002; 62(9): 2522 - 2530. [Abstract] [Full Text] [PDF]
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 T. Niki, T. Kohno, S. Iba, Y. Moriya, Y. Takahashi, M. Saito, A. Maeshima, T. Yamada, Y. Matsuno, M. Fukayama, et al. Frequent Co-Localization of Cox-2 and Laminin-5 {gamma}2 Chain at the Invasive Front of Early-Stage Lung Adenocarcinomas Am. J. Pathol., March 1, 2002; 160(3): 1129 - 1141. [Abstract] [Full Text] [PDF]
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