Gastrin/CCK B G protein-coupled receptors have been shown to mediate proliferation stimulated by their endogenous ligands. The present study demonstrates the proliferative effect of arachidonic acid on AR4-2J cells. Gastrin induces an [ 3 H]arachidonic-acid release in a dose-dependent manner. The us
Calcium-independent phospholipase A2 through arachidonic acid mobilization is involved in Caco-2 cell growth
✍ Scribed by Teresa Sanchez; Juan J. Moreno
- Publisher
- John Wiley and Sons
- Year
- 2002
- Tongue
- English
- Weight
- 123 KB
- Volume
- 193
- Category
- Article
- ISSN
- 0021-9541
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✦ Synopsis
Abstract
Several studies indicate that phospholipase A~2~ (PLA~2~) expression and/or activation account for the high levels of arachidonic acid (AA) detected in cancer and, together with the elevated expression of cyclooxygenase‐2, lead to cell proliferation and tumor formation. Using Caco‐2 cells, a human colorectal carcinoma cell, we studied the role of high‐molecular‐weight PLA~2~s, cytosolic PLA~2~ (cPLA~2~), and calcium‐independent PLA~2~ (iPLA~2~) in the AA cascade and in cell growth. Treatment with an antisense oligonucleotide against cPLA~2~α decreased [^3^H]AA release induced by ionophore A23187 or by a phorbol ester but did not affect the release of [^3^H]AA, [^3^H]thymidine incorporation, or Caco‐2 growth induced by fetal calf serum (FCS). However, these parameters were significantly modified by iPLA~2~ inhibitors and by an antisense oligonucleotide against iPLA~2~β. Our results show that iPLA~2~ was involved in AA release and the subsequent prostaglandin production induced by serum. Moreover, these data indicate that iPLA~2~ may be involved in the signaling pathways involved in the control of Caco‐2 proliferation. © 2002 Wiley‐Liss, Inc.
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