第二型環氧酵素(COX-2)基因對於非小細胞肺癌之醣化酵素基因與Lewis涎化抗原表現之調控(2/3)

Products of anerrant glycosylation may facilitate tumor cell invasion into blood stream,
attachment to endothelial cells and escape from host immuno-surveillance. Our previous studies
had demonstrated the prognostic implication of sialyl Lewis antigens (sLe x and sLe a ) for lung
cancer. Lung cancers overexpressing sLe antigens tend to have higher chance of recurrence and
metastasis. Using multiplex PCR to evaluate the expression of sialyltransferase(ST) and
fucosyltransferase(FucT) gene families in lung cancer, we have demonstrated that tumors with
overexpression of ST3GalIII and FucTIII 、IV 、VI 、VII are closely related to expression of sialyl
Lewis antigens, and to cancer recurrence and postoperative death. Cell line study revealed that
cell lines (CL1-5 , CL1-5 F4) with high invasiveness and metastasis ability expressed more STs
and FucTs than parent cell line (CL1-0 and CL1-1). This panel of cell lines posses incremental
expression of cyclooxygenase-2 (COX-2), positively correlate with the degree of invasiveness.
COX-2 involves many aspects of cancer cell biology, including cell growth, antiapoptosis,
angiogenesis, cell motility and invasion. Evidence has been demonstrated in colon cancer cell
lines that, COX-2 can promote cancer metastasis through expression of certain
glycosyltransferase genes and sialyl Lewis antigens. Up to now, the mechanisms of how COX-2
regulate the expression of GT genes has never been reported. We thus propose a three-year study
to comprehensively study the expression of COX-2, the receptors of COX-2 products (i.e.,
prostglandins, PG), EP1-4 and PPAR摯瑬敳獩 ，γ ，δ in lung cancer. And correlate with expression status
of GT genes and sLe antigens completed in our previous work. The study will identify specific
glycosyltransferase genes, and, probably sepcific EP or PPAR related to COX-2 expression. The
regulatory mechanism of COX-2 on these GT genes will then be explored.