Upregulation of thromboxane synthase in human colorectal carcinoma and the cancer cell proliferation by thromboxane A2.
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.
Sakai
Hideki
H
Department of Pharmaceutical Physiology, Graduate School of Medical and Pharmaceutical Sciences, University of Toyama, Japan. sakaih@pha.u-toyama.ac.jp
Suzuki
Tomoyuki
T
Takahashi
Yuji
Y
Ukai
Masashi
M
Tauchi
Katsunori
K
Fujii
Takuto
T
Horikawa
Naoki
N
Minamimura
Tetsuji
T
Tabuchi
Yoshiaki
Y
Morii
Magotoshi
M
Tsukada
Kazuhiro
K
Takeguchi
Noriaki
N
D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D009841:Oligonucleotides / Q000494:pharmacology; D013928:Thromboxane A2 / Q000494:pharmacology*; D013930:Thromboxane-A Synthase / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects*
D009841:Oligonucleotides; D013928:Thromboxane A2; D013930:Thromboxane-A Synthase