Upregulation of thromboxane synthase in human colorectal carcinoma and the cancer cell proliferation by thromboxane A2

FEBS Lett. 2006 Jun 12;580(14):3368-74. doi: 10.1016/j.febslet.2006.05.007. Epub 2006 May 11.

Abstract

Tumor growth of colorectal cancers accompanies upregulation of cyclooxygenase-2, which catalyzes a conversion step from arachidonic acid to prostaglandin H(2) (PGH(2)). Here, we compared the expression levels of thromboxane synthase (TXS), which catalyzes the conversion of PGH(2) to thromboxane A(2) (TXA(2)), between human colorectal cancer tissue and its accompanying normal mucosa. It was found that TXS protein was consistently upregulated in the cancer tissues from different patients. TXS was also highly expressed in human colonic cancer cell lines. Depletion of TXS protein by the antisense oligonucleotide inhibited proliferation of the cancer cells. This inhibition was rescued by the direct addition of a stable analogue of TXA(2). The present results suggest that overexpression of TXS and subsequent excess production of TXA(2) in the cancer cells may be involved in the tumor growth of human colorectum.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Colorectal Neoplasms / enzymology*
  • Colorectal Neoplasms / pathology
  • Humans
  • Immunohistochemistry
  • Oligonucleotides / pharmacology
  • Thromboxane A2 / pharmacology*
  • Thromboxane-A Synthase / metabolism*
  • Up-Regulation / drug effects*

Substances

  • Oligonucleotides
  • Thromboxane A2
  • Thromboxane-A Synthase