Downregulation of a human colonic sialyltransferase by a secondary bile acid and a phorbol ester

Ming Li, Ravi Vemulapalli, Asad Ullah, Leighton Izu, Michael E. Duffey, Michael P Lance

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Fecal constituents such as bile acids and increased sialylation of membrane glycoproteins by α-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 μmol/l), a secondary bile acid, and TPA (20 ng/ml) decreased expression of an ~100-kDa glycoprotein bearing α-2,6-linked sialic acid in a colon cancer cell line (T84) in vitro. HST6N-1 mRNA levels were reduced ~80% by treatment (≤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, α-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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume274
Issue number3 37-3
StatePublished - Mar 1998
Externally publishedYes

Fingerprint

Sialyltransferases
Phorbol Esters
Tetradecanoylphorbol Acetate
Bile Acids and Salts
Deoxycholic Acid
Down-Regulation
Up-Regulation
Cholates
Membrane Glycoproteins
N-Acetylneuraminic Acid
Enzymes
Colonic Neoplasms
Protein Kinase C
Colorectal Neoplasms
Glycoproteins
Carcinogenesis
Neoplasm Metastasis
Cell Line
Messenger RNA
beta-D-galactoside alpha 2-6-sialyltransferase

Keywords

  • Colorectal neoplasia
  • Gene expression regulation
  • Glycosyltransferase expression

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology
  • Physiology (medical)

Cite this

Downregulation of a human colonic sialyltransferase by a secondary bile acid and a phorbol ester. / Li, Ming; Vemulapalli, Ravi; Ullah, Asad; Izu, Leighton; Duffey, Michael E.; Lance, Michael P.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 274, No. 3 37-3, 03.1998.

Research output: Contribution to journalArticle

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abstract = "Fecal constituents such as bile acids and increased sialylation of membrane glycoproteins by α-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 μmol/l), a secondary bile acid, and TPA (20 ng/ml) decreased expression of an ~100-kDa glycoprotein bearing α-2,6-linked sialic acid in a colon cancer cell line (T84) in vitro. HST6N-1 mRNA levels were reduced ~80{\%} by treatment (≤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, α-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.",
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AU - Li, Ming

AU - Vemulapalli, Ravi

AU - Ullah, Asad

AU - Izu, Leighton

AU - Duffey, Michael E.

AU - Lance, Michael P

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N2 - Fecal constituents such as bile acids and increased sialylation of membrane glycoproteins by α-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 μmol/l), a secondary bile acid, and TPA (20 ng/ml) decreased expression of an ~100-kDa glycoprotein bearing α-2,6-linked sialic acid in a colon cancer cell line (T84) in vitro. HST6N-1 mRNA levels were reduced ~80% by treatment (≤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, α-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.

AB - Fecal constituents such as bile acids and increased sialylation of membrane glycoproteins by α-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 μmol/l), a secondary bile acid, and TPA (20 ng/ml) decreased expression of an ~100-kDa glycoprotein bearing α-2,6-linked sialic acid in a colon cancer cell line (T84) in vitro. HST6N-1 mRNA levels were reduced ~80% by treatment (≤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, α-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.

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