title: Upregulation of thromboxane synthase in human colorectal carcinoma and the cancer cell proliferation by thromboxane A2.
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.
authors.affiliation: Department of Pharmaceutical Physiology, Graduate School of Medical and Pharmaceutical Sciences, University of Toyama, Japan. sakaih@pha.u-toyama.ac.jp
authors.forename: Hideki
authors.initials: H
authors.lastname: Sakai
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Suzuki
authors.forename: Yuji
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Masashi
authors.initials: M
authors.lastname: Ukai
authors.forename: Katsunori
authors.initials: K
authors.lastname: Tauchi
authors.forename: Takuto
authors.initials: T
authors.lastname: Fujii
authors.forename: Naoki
authors.initials: N
authors.lastname: Horikawa
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Minamimura
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Tabuchi
authors.forename: Magotoshi
authors.initials: M
authors.lastname: Morii
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tsukada
authors.forename: Noriaki
authors.initials: N
authors.lastname: Takeguchi
mesh_terms: 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*
chemical_list: D009841:Oligonucleotides; D013928:Thromboxane A2; D013930:Thromboxane-A Synthase