Abstract
Fecal constituents such as bile acids and increased sialylation of membrane glycoproteins by alpha-2,6-sialyltransferase (HST6N-1) may contribute to colorectal tumorigenesis. We hypothesized that bile acids and phorbol ester [12-O-tetradecanoylphorbol-13-acetate (TPA)] would upregulate HST6N-1 in colonic cells. However, deoxycholate (DOC) (300 mumol/l), a secondary bile acid, and TPA (20 ng/ml) decreased expression of an approximately 100-kDa glycoprotein bearing alpha-2,6-linked sialic acid in a colon cancer cell line (T84) in vitro. HST6N-1 mRNA levels were reduced approximately 80% by treatment (< or = 24 h) with DOC or TPA but not by cholate, a primary bile acid. Treatment (24 h) with DOC or TPA decreased activity of this enzyme to 30% and 13% of control, respectively. These effects of DOC and TPA were transcriptional and were mediated by Ca2+ and protein kinase C, respectively. Thus DOC and TPA both downregulated, and did not upregulate, alpha-2,6-sialyltransferase expression in vitro, but by different transduction pathways. As colorectal tumors grow, their progressive removal from the fecal milieu that normally downregulates this enzyme may favor invasion and metastasis.
References
Sep 30, 1992·International Journal of Cancer. Journal International Du Cancer·X P HuangM Castagna
May 10, 1991·International Journal of Cancer. Journal International Du Cancer·H SaitoM Tsuchiya
Aug 1, 1991·Biochemical Society Transactions·H SchachterR Dunn
Sep 1, 1989·The Journal of Clinical Investigation·K DharmsathaphornH V Ammon
Oct 16, 1989·Biochemical and Biophysical Research Communications·P LanceJ T Lau
Dec 15, 1988·Biochemical and Biophysical Research Communications·K A MasriM N Fukuda
Jan 1, 1988·Cancer Letters·J StadlerW R Bruce
Oct 1, 1970·Chemistry and Physics of Lipids·S Roseman
Sep 1, 1982·Proceedings of the National Academy of Sciences of the United States of America·W H LamersH M Meisner
Oct 1, 1995·Clinical Science·M LiP Lance
Nov 1, 1993·The Journal of Clinical Investigation·D C DevorM E Duffey
Sep 1, 1993·Cellular Immunology·P HaussA Fischer
Dec 1, 1993·European Journal of Clinical Investigation·I P van MunsterF M Nagengast
Nov 1, 1993·The Journal of Clinical Investigation·M Field
Jan 1, 1993·Gastroenterology·E BayerdörfferG Paumgartner
Jan 1, 1996·The Journal of Laboratory and Clinical Medicine·L L ShekelsS B Ho
May 1, 1996·Gastroenterology·R S BresalierJ C Byrd
Jun 1, 1996·In Vitro Cellular & Developmental Biology. Animal·M P MoyerL R Tanzer