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. 2006 Feb;20(2):386-8.
doi: 10.1096/fj.05-4331fje. Epub 2005 Nov 30.

Sphingosine kinase 1 is up-regulated in colon carcinogenesis

Toshihiko Kawamori  1 , Walid Osta, Korey R Johnson, Benjamin J Pettus, Jacek Bielawski, Takuji Tanaka, Michael J Wargovich, Bandaru S Reddy, Yusuf A Hannun, Lina M Obeid, Daohong Zhou
Affiliations

Sphingosine kinase 1 is up-regulated in colon carcinogenesis

Toshihiko Kawamori et al. FASEB J. 2006 Feb.

Abstract

Sphingosine kinase 1 (SK1) phosphorylates sphingosine to form sphingosine 1-phosphate (S1P), which has the ability to promote cell proliferation and survival and stimulate angiogenesis. The SK1/S1P pathway also plays a critical role in regulation of cyclooxygenase-2 (COX-2), a well-established pathogenic factor in colon carcinogenesis. Therefore, we examined the expression of SK1 and COX-2 in rat colon tumors induced by azoxymethane (AOM) and the relationship of these two proteins in normal and malignant intestinal epithelial cells. Strongly positive SK1 staining was found in 21/28 (75%) of rat colon adenocarcinomas induced by AOM, whereas no positive SK1 staining was observed in normal mucosa. The increase in SK1 and COX-2 expression in AOM-induced rat colon adenocarcinoma was confirmed at the level of mRNA by real-time RT-PCR. In addition, it was found that 1) down-regulation of SK1 in HT-29 human colon cancer cells by small interfering RNA (siRNA) decreases COX-2 expression and PGE2 production; 2) overexpression of SK1 in RIE-1 rat intestinal epithelial cells induces COX-2 expression; and 3) S1P stimulates COX-2 expression and PGE2 production in HT-29 cells. These results suggest that the SK1/S1P pathway may play an important role in colon carcinogenesis, in part, by regulating COX-2 expression and PGE2 production.

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