論文名稱:

離胺基氧化酶功能性多型性對口腔鱗狀細胞上皮癌表型影響之探討

 

The phenotypic influences of Lysyl Oxidase (LOX) functional polymorphism on oral squamous cell carcinoma

研究生:

顧迪璿  Ti-Hsuan Ku

 

(以作者名查詢陽明大學館藏系統)

 

(以作者名查詢全國圖書書目資訊網)

指導教授:

張國威  Kuo-Wei Chang

        學位類別:

碩士

        學校名稱:

國立陽明大學

系所名稱:

口腔生物研究所

            學號:

39317003

          學年度:

94

          語文別:

中文

          出版年:

95

關鍵字:

口腔癌  oral cancer

 

離胺基氧化酶  lysyl oxidase

 

單核苷酸多型性  single nucleotide polymorphism

全文說明:

(本論文 20080716 對校內公開)

 

電子全文

        論文頁數:

77

摘要:

在台灣口腔癌於男性前十大癌症發生率及死亡率高居第四位。本實驗室先前研究發現離胺基氧化酶 (lysyl oxidaseLOX)在癌組織有過量表現的趨勢。近來亦有研究發現,在乳癌細胞株、肺癌組織、腎細胞惡性腫瘤組織等皆可見LOX表現增加,並會加強乳癌侵襲及轉移的能力,而在某些皮膚癌及頭頸癌之研究可見LOX表現之降低。LOX為一活化態為32kDa的蛋白質,在銅離子的幫助下,能夠在細胞外基質(extracellular matrix),氧化膠原蛋白(collagen)和彈性蛋白(elastin)上特殊的離胺酸殘基,使膠原蛋白和彈性蛋白形成共價鍵結,亦另有其他功能。在LOX基因473鹼基處存在有GA的多型性,此多型性出現頻率極高,會造成胺基酸Arg158的位置變為Gln,與口腔黏膜纖維化(oral submucous fibrosis)及胃癌的發生具有相關性,本研究將SAS口腔癌細胞經野生型LOXG473A LOX轉染所建立之穩定細胞株發現,具此多型性之LOX酵素活性較野生型LOX酵素活性為高,但野生型LOX基因似有促進細胞生長的功能,而多型性LOX則否此外,不論野生型LOX酵素或多型性LOX酵素皆能促使口腔癌細胞增加anchorage-independent之能力。當野生型LOX酵素受β-APN抑制活性時,其促使口腔癌細胞移行及侵襲之能力較多型性LOX酵素明顯。因此初步推測野生型LOX基因於口腔癌之高度表現可能有較高的促癌能力;且野生型LOX基因表現之調降對口腔癌細胞擴散,有較顯著之貢獻,LOX致癌角色因多型性之存在而更加複雜。

 

Oral squamous cell carcinoma (OSCC) is the 4th leading malignancy in incidence and mortality rate in male population of Taiwan. Previously, our laboratory has found the high expression of lysyl oxidase (LOX) in OSCC tissues. The roles of LOX as an oncogene or suppressor gene have been very controversial. Increase of LOX expression has been found in breast, lung, renal and head and neck carcinomas. Such increase seemed to be associated with the invasion and metastasis of breast carcinoma cells. On the contrary, decrease of LOX expression has been found in gastric, skin and head and neck carcinomas. Active LOX is a 32 kDa protein, which is activated by copper ion binding that catalyzes the oxidation of lysine in collagen and elastin. This results in covalent cross-linking between molecules and remodeling of extracellular matrix. LOX may also exhibit additional functions that were not clearly characterized. There is a G to A transition in nt. 473, which causes the Arg158Gln change in LOX coding sequence. This polymorphism was linked to the susceptibility of oral submucous fibrosis and the occurrence of gastric carcinoma. I generated stable clones in SAS OSCC cells with wild type (WT) or LOX Arg158Gln transfection. Analysis indicated that LOX Arg158Gln clones had higher LOX activity than WT clones. However, WT clones had higher proliferation rate relative to LOX Arg158Gln clones. Both WT and LOX Arg158Gln clones had an increase in anchorage-independent growth relative to parental cells. With β-APN treatment that inhibited LOX activity at the same level, increase of in vitro migration and invasion was more prominently seen in WT clones than that in LOX Arg158Gln clones. This research concludes preliminarily that the increase expression in WT LOX may potentiate neoplastic process through increase of proliferation. Down-regulation of WT LOX may be advantageous for the dissemination of neoplastic cells through the increase of mobility and invasion. The role of LOX in carcinogenesis is complicated by the functional polymorphism.