余忠仁2006-07-262018-07-112006-07-262018-07-112005http://ntur.lib.ntu.edu.tw//handle/246246/23686癌細胞之醣化過程異於正常細胞，特殊之醣化抗原(如Lewis 涎化抗原)表現有利其脫離 源發病灶，入侵血管，並逃避宿主之免疫系統攻擊。在吾人先前之研究中,已證實肺癌之異 常醣化過程（Lewis 涎化抗原之產生）均與肺癌病患術後之預後有關，而利用multiplex PCR 探討肺癌之醣化酵素基因表現（包括sialyltransferase ，STs ；與fucosyltransferase ，FucTs ）， ST3GalIII 、FucTIII 、IV 、VI 、VII 之表現量與Lewis 涎化抗原之產生及肺癌之遠處轉移、 術後存活有明顯相關。細胞株之研究亦顯示侵犯力高易轉移的細胞株（CL1-5 ，CL1-5 F4 ）， 其STs 與FucTs 之表現量高於侵犯力弱的母細胞株（CL1-0 、CL1-1 ）。而此一系列之細胞株 呈現次第增加的第二型環氧酵素表現量。第二型環氧酵素被認為與腫瘤生長、反細胞凋亡、 血管生成、細胞移動與侵犯能力有關，有初步證據證實再大腸癌細胞，第二型環氧酵素基 因可以藉由調控某些醣化酵素基因而表現出Lewis 涎化抗原，促進癌細胞轉移。其調控機 轉至今仍無相關文獻探討。本三年研究計劃之目的為：(1)廣泛而完整的探討第二型環氧酵 素基因與其產物（前列腺素，尤其是PGE2 ，PGI2 ）之受體（EP1-4 ；PPAR摯瑬敳獩 ，γ ，δꅞ 在肺 癌之表現情形以及與醣化酵素基因、以及Lewis 涎化抗原表現之相關聯性；(2)對於由(1)所 選出具臨床意義之EP ，PPAR 受體與醣化酵素基因，本研究將著手探討第二型環氧酵素對 這些醣化酵素基因表現之訊息傳遞調控機轉。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.application/pdf117818 bytesapplication/pdfzh-TW國立臺灣大學醫學院內科肺癌醣化酵素基因Lewis 涎化抗原第二型環氧酵素Lung cancerglycosyltransferasesialyl Lewis antigencyclooxygenase-2[SDGs]SDG3reporthttp://ntur.lib.ntu.edu.tw/bitstream/246246/23686/1/932314B002058.pdf