Li M, Vemulapalli R, Ullah A, Izu L, Duffey M E, Lance P
Department of Medicine, Buffalo Veterans Affairs Medical Center, New York, USA.
Am J Physiol. 1998 Mar;274(3):G599-606. doi: 10.1152/ajpgi.1998.274.3.G599.
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.
粪便成分如胆汁酸以及α-2,6-唾液酸转移酶（HST6N-1）导致的膜糖蛋白唾液酸化增加可能与结直肠癌发生有关。我们推测胆汁酸和佛波酯[12-O-十四酰佛波醇-13-乙酸酯（TPA）]会上调结肠细胞中的HST6N-1。然而，在体外，二级胆汁酸脱氧胆酸盐（DOC）（300μmol/L）和TPA（20 ng/ml）降低了结肠癌细胞系（T84）中一种带有α-2,6-连接唾液酸的约100 kDa糖蛋白的表达。用DOC或TPA处理（≤24小时）可使HST6N-1 mRNA水平降低约80%，但初级胆汁酸胆酸盐则无此作用。用DOC或TPA处理24小时分别使该酶的活性降至对照的30%和13%。DOC和TPA的这些作用是转录性的，分别由Ca2+和蛋白激酶C介导。因此，DOC和TPA在体外均下调而非上调α-2,6-唾液酸转移酶的表达，但通过不同的转导途径。随着结直肠癌的生长，肿瘤逐渐脱离通常会下调该酶的粪便环境，这可能有利于肿瘤的侵袭和转移。
