Journal Article

Cyclooxygenase-2 expression in human pancreatic adenocarcinomas

Michele T. Yip-Schneider, Darlene S. Barnard, Steven D. Billings, Liang Cheng, Douglas K. Heilman, Amy Lin, Steven J. Marshall, Pamela L. Crowell, Mark S. Marshall and Christopher J. Sweeney

in Carcinogenesis

Volume 21, issue 2, pages 139-146
Published in print February 2000 | ISSN: 0143-3334
Published online February 2000 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/21.2.139
Cyclooxygenase-2 expression in human pancreatic adenocarcinomas

More Like This

Show all results sharing this subject:

  • Clinical Cytogenetics and Molecular Genetics

GO

Show Summary Details

Preview

Cyclooxygenase-2 (COX-2) expression is up-regulated in several types of human cancers and has also been directly linked to carcinogenesis. To investigate the role of COX-2 in pancreatic cancer, we evaluated COX-2 protein expression in primary human pancreatic adenocarcinomas (n = 23) and matched normal adjacent tissue (n = 11) by immunoblot analysis. COX-2 expression was found to be significantly elevated in the pancreatic tumor specimens compared with normal pancreatic tissue. To examine whether the elevated levels of COX-2 protein observed in pancreatic tumors correlated with the presence of oncogenic K-ras, we determined the K-ras mutation status in a subset of the tumors and corresponding normal tissues. The presence of oncogenic K-ras did not correlate with the level of COX-2 protein expressed in the pancreatic adenocarcinomas analyzed. These observations were also confirmed in a panel of human pancreatic tumor cell lines. Furthermore, in the pancreatic tumor cell line expressing the highest level of COX-2 (BxPC-3), COX-2 expression was demonstrated to be independent of Erk1/2 activation. The lack of correlation between COX-2 and oncogenic K-ras expression suggests that Ras activation may not be sufficient to induce COX-2 expression in pancreatic tumor cells and that the aberrant activation of signaling pathways other than Ras may be required for up-regulating COX-2 expression. We also report that the COX inhibitors sulindac, indomethacin and NS-398 inhibit cell growth in both COX-2-positive (BxPC-3) and COX-2-negative (PaCa-2) pancreatic tumor cell lines. However, suppression of cell growth by indomethacin and NS-398 was significantly greater in the BxPC-3 cell line compared with the PaCa-2 cell line (P = 0.004 and P < 0.001, respectively). In addition, the three COX inhibitors reduce prostaglandin E2 levels in the BxPC-3 cell line. Taken together, our data suggest that COX-2 may play an important role in pancreatic tumorigenesis and therefore be a promising chemotherapeutic target for the treatment of pancreatic cancer.

Keywords: COX, cyclooxygenase; DMSO, dimethylsulfoxide; Erk1/2 MAP kinase, extracellular signal-regulated kinase 1 and 2 mitogen-activated protein kinase; FCS, fetal calf serum; LPS, lipopolysaccharide; MEK, MAP kinase kinase; NSAIDS, non-steroidal anti-inflammatory drugs; NSCLC, non-small cell lung cancer; PGE2, prostaglandin E2; PMA, phorbol 12-myristate 13-acetate.

Journal Article.  5865 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.