Cyclooxygenase-2 expression in human pancreatic adenocarcinomas

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

Research output: Contribution to journalArticle

244 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)139-146
Number of pages8
JournalCarcinogenesis
Volume21
Issue number2
StatePublished - 2000

Fingerprint

Cyclooxygenase 2
Adenocarcinoma
Tumor Cell Line
Neoplasms
Pancreatic Neoplasms
Cell Line
Indomethacin
Carcinogenesis
Sulindac
Proteins
Growth
Dinoprostone

ASJC Scopus subject areas

  • Cancer Research

Cite this

Yip-Schneider, M., Barnard, D. S., Billings, S. D., Cheng, L., Heilman, D. K., Lin, A., ... Sweeney, C. J. (2000). Cyclooxygenase-2 expression in human pancreatic adenocarcinomas. Carcinogenesis, 21(2), 139-146.

Cyclooxygenase-2 expression in human pancreatic adenocarcinomas. / Yip-Schneider, Michele; Barnard, Darlene S.; Billings, Steven D.; Cheng, Liang; Heilman, Douglas K.; Lin, Amy; Marshall, Steven J.; Crowell, Pamela L.; Marshall, Mark S.; Sweeney, Christopher J.

In: Carcinogenesis, Vol. 21, No. 2, 2000, p. 139-146.

Research output: Contribution to journalArticle

Yip-Schneider, M, Barnard, DS, Billings, SD, Cheng, L, Heilman, DK, Lin, A, Marshall, SJ, Crowell, PL, Marshall, MS & Sweeney, CJ 2000, 'Cyclooxygenase-2 expression in human pancreatic adenocarcinomas', Carcinogenesis, vol. 21, no. 2, pp. 139-146.
Yip-Schneider M, Barnard DS, Billings SD, Cheng L, Heilman DK, Lin A et al. Cyclooxygenase-2 expression in human pancreatic adenocarcinomas. Carcinogenesis. 2000;21(2):139-146.
Yip-Schneider, Michele ; Barnard, Darlene S. ; Billings, Steven D. ; Cheng, Liang ; Heilman, Douglas K. ; Lin, Amy ; Marshall, Steven J. ; Crowell, Pamela L. ; Marshall, Mark S. ; Sweeney, Christopher J. / Cyclooxygenase-2 expression in human pancreatic adenocarcinomas. In: Carcinogenesis. 2000 ; Vol. 21, No. 2. pp. 139-146.
@article{0acafae6162448d1a2c4531aec1517ad,
title = "Cyclooxygenase-2 expression in human pancreatic adenocarcinomas",
abstract = "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.",
author = "Michele Yip-Schneider and Barnard, {Darlene S.} and Billings, {Steven D.} and Liang Cheng and Heilman, {Douglas K.} and Amy Lin and Marshall, {Steven J.} and Crowell, {Pamela L.} and Marshall, {Mark S.} and Sweeney, {Christopher J.}",
year = "2000",
language = "English",
volume = "21",
pages = "139--146",
journal = "Carcinogenesis",
issn = "0143-3334",
publisher = "Oxford University Press",
number = "2",

}

TY - JOUR

T1 - Cyclooxygenase-2 expression in human pancreatic adenocarcinomas

AU - Yip-Schneider, Michele

AU - Barnard, Darlene S.

AU - Billings, Steven D.

AU - Cheng, Liang

AU - Heilman, Douglas K.

AU - Lin, Amy

AU - Marshall, Steven J.

AU - Crowell, Pamela L.

AU - Marshall, Mark S.

AU - Sweeney, Christopher J.

PY - 2000

Y1 - 2000

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0033963927&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033963927&partnerID=8YFLogxK

M3 - Article

VL - 21

SP - 139

EP - 146

JO - Carcinogenesis

JF - Carcinogenesis

SN - 0143-3334

IS - 2

ER -