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Carcinogenesis

Transcription of Cyclooxygenase-2 Is Enhanced in Transformed Mammary Epithelial Cells

Kotha Subbaramaiah, Nitin Telang, John T. Ramonetti, Ruriko Araki, Bethany DeVito, Babette B. Weksler and Andrew J. Dannenberg
Kotha Subbaramaiah
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Nitin Telang
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John T. Ramonetti
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Ruriko Araki
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Bethany DeVito
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Babette B. Weksler
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Andrew J. Dannenberg
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DOI:  Published October 1996
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Abstract

Cancers form more prostaglandins than the normal tissues from which they arise. Cyclooxygenase-2 (prostaglandin H synthase-2, PGHS-2, EC 1.14.99.1), an enzyme that catalyzes the formation of prostaglandins from arachidonic acid, is inducible in epithelial cells. We investigated whether transformation of mammary cells was associated with up-regulation of Cox-2 as a basis for increased production of prostaglandin E2 (PGE2) by these cells. This hypothesis was tested in two pairs of mammary cell lines between which the mode of transformation (viral versus oncogene) differed. Virally transformed RIII/Pr1 cells, which are highly tumorigenic in mice, produced markedly increased amounts of PGE2 compared to virally initiated RIII/MG cells, a weakly tumorigenic strain. Cox-2 mRNA and protein were increased concomitantly in RIII/Pr1 cells. Similarly, Ras-induced transformation of C57/MG cells resulted in increased levels of Cox-2 mRNA and protein and increased production of PGE2. Nuclear run-offs revealed increased rates of Cox-2 transcription in the virally transformed and oncogene-transformed cell lines. Transient transfection experiments demonstrated that the oncogenes src and ras up-regulated Cox-2 promoter activity. Src-mediated up-regulation of Cox-2 promoter activity was suppressed by dominant negative ras. Our data indicate that cellular transformation is associated with enhanced transcription of Cox-2 and increased production of PGE2.

Footnotes

  • ↵1 This work was supported by Department of Army Grant DAMD 17-94-J4208 (to N. T.), NIH Grants CA68136 (to A. J. D.) and PO1CA29502 (to N. T.), and a NIH SCOR in Thrombosis HL 18828 (to B. B. W.).

  • ↵2 To whom requests for reprints should be addressed, at Division of Digestive Diseases, Room F-231, The New York Hospital-Cornell Medical Center, New York, NY 10021.

  • Received April 29, 1996.
  • Accepted August 1, 1996.
  • ©1996 American Association for Cancer Research.
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October 1996
Volume 56, Issue 19
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Transcription of Cyclooxygenase-2 Is Enhanced in Transformed Mammary Epithelial Cells
Kotha Subbaramaiah, Nitin Telang, John T. Ramonetti, Ruriko Araki, Bethany DeVito, Babette B. Weksler and Andrew J. Dannenberg
Cancer Res October 1 1996 (56) (19) 4424-4429;

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Transcription of Cyclooxygenase-2 Is Enhanced in Transformed Mammary Epithelial Cells
Kotha Subbaramaiah, Nitin Telang, John T. Ramonetti, Ruriko Araki, Bethany DeVito, Babette B. Weksler and Andrew J. Dannenberg
Cancer Res October 1 1996 (56) (19) 4424-4429;
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