RT Journal Article
SR Electronic
T1 Transcription of Cyclooxygenase-2 Is Enhanced in Transformed Mammary Epithelial Cells
JF Cancer Research
JO Cancer Res
FD American Association for Cancer Research
SP 4424
OP 4429
VO 56
IS 19
A1 Subbaramaiah, Kotha
A1 Telang, Nitin
A1 Ramonetti, John T.
A1 Araki, Ruriko
A1 DeVito, Bethany
A1 Weksler, Babette B.
A1 Dannenberg, Andrew J.
YR 1996
UL http://cancerres.aacrjournals.org/content/56/19/4424.abstract
AB 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. ©1996 American Association for Cancer Research.