論文名稱:

類胰島素生長因子之依附性在類胰島素生長因子結合蛋白第五型調節SAS 口腔癌細胞株表型之角色

 

The roles of IGF-dependent mechanisms in IGFBP-5-mediated phenotypic regulation of SAS oral cancer cells

研究生:

石尹華  Yin-Hua Shih

 

(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:

林姝君  Shu-Chun Lin

        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:

39317001

          學年度:

94

          語文別:

中文

          出版年:

95

關鍵字:

類胰島素生長因子結合蛋白第五型  IGFBP-5

 

類胰島素生長因子  IGF

 

細胞生長  cell proliferation

 

細胞移行  cell migration

全文說明:

電子全文

        論文頁數:

59

摘要:

類胰島素生長因子Insulin-like growth factors (IGF-I and IGF-II)

 

是在人類循環系統中主要的生長促進因子,在各個不同種類的細胞中

 

扮演著促使細胞存活、增生及分化的角色,其與促使癌症的生成也有

 

關聯,類胰島素生長因子會促進癌細胞的細胞分裂以及使其對抗細胞

 

凋亡以及促進細胞的移行。因此近年來研究致力於抑制IGF 的作用以

 

為癌症治療。有六種不同的類胰島素生長因子結合蛋白IGF-binding

 

proteins (IGFBPs) 會與IGF 結合,藉此調控IGF 的半衰期以及對細胞

 

的刺激作用;然而IGFBP 不僅具有依附IGF 的功能(IGF-dependent)

 

有些還存在不依附IGF 的作用機制(IGF-independent)。文獻指出

 

IGFBP-5 對於不同種類的癌細胞之影響,大致有促進以及抑制腫瘤生

 

成兩種互為衝突之作用。先前在實驗室研究發現,IGFBP-5 會抑制

 

OECM-1 SAS 口腔癌細胞株增生,促使其移行,但不確定其與IGF

 

依附性之關係。本研究針對IGFBP-5-EGFP 蛋白質N 端的IGF-binding

 

site 作五個胺基酸之突變或是將大部分的IGFBP-5 片段刪除,剩下C

 

端蛋白質區域的部分,再將其大量表現於SAS 口腔癌細胞株中,探

 

WT IGFBP-5-EGFP 是透過IGF-dependent 或是IGF-independent

 

徑使SAS 細胞表型改變。結果發現,∆ IGFBP-5-EGFP 促使SAS

 

癌細胞增生,顯示IGF 結合區以外之N 端尚有抑制增生之區域。

 

WT IGFBP-5-EGFP 經由IGF-dependent 路徑增進細胞移行

 

Insulin-like growth factors (IGF-I and IGF-II) are the major growth

 

promoting growth factors in the circulation system. These ligands

 

stimulate cell survival and promote proliferation and differentiation of

 

different cell types. IGF is also related to cancer formation. It might

 

induce proliferation and anti-apoptosis in cancer cells. Thereby, blockage

 

of IGF has been tested for an anti-cancer regimen. There are six IGFBPs

 

in IGFBP gene family. IGFBPs prolong half-life of the IGFs in the

 

circulation and inhibit their metabolic effects by preventing them from

 

binding to their receptors. IGFBP-5 also exhibit IGF-independent action

 

that might drive variable effects. Controversial phenotypic impacts of

 

IGFBP-5 against different types of cells were shown. The discrepancies

 

in phenotypic impacts may be resulted from the differential influences

 

from IGF-dependent and IGF-independent functions. Previously, our

 

laboratory has found that IGFBP-5 could inhibit OECM-1 and SAS oral

 

cancer cell proliferation and promote theirs migration. However, such

 

regulation is IGF-dependent or IGF-independent needs further

 

clarification. In this study, I plan to distinguish the IGF-dependent and

 

IGF-independent cellular impacts in oral cancer cells using mutation

 

constructs. I generated a mutant construct that disrupts IGF binding site, a

 

construct with N-terminal deletion and vector alone plasmid. Transient

 

transfection and comparison analysis indicated that the deletion construct

 

enhance cell proliferation indicating and existence of domains other than

 

IGF-binding site lie in N terminal that against growth. Besides, the

 

induction of cell migration ability mediated by IGFBP-5 was

 

IGF-dependent.