論文名稱:

口腔上皮癌化過程與分化過程調控IGFBP-5基因表現之探討

 

Regulation of IGFBP-5 Expression during Tumorigenesis and Oral Keratinocyte Differentiation

研究生:

王瓊珮  Chiung-Pei Wang

 

(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:

870H04

          學年度:

88

          語文別:

中文

          出版年:

89

關鍵字:

IGFBP-5基因  IGFBP-5

 

分化  Differentiation

 

癌化  Tumorigenesis

        論文頁數:

73

摘要:

根據行政院衛生署保健處統計,在台灣地區口腔癌位居男性十大惡性腫瘤發生率排名第五位,而90%的口腔惡性腫瘤為口腔鱗狀細胞癌(oral squamous cell carcinoma, OSCC)OSCC的形成一般生成因素認為和嚼食檳榔,吸菸等環境因子有關,這些環境因子會直接或間接地造成基因表現的改變,進而促成腫瘤生成。本研究中利用減算雜交法(subtractive hybridization)得到 135個表現於人類正常口腔組織而在口腔腫瘤組織缺失的基因,從中挑選CL100BRCA2ST13C/EBPIGFBP-rP1以及IGFBP-5六個基因,在八個鱗狀上皮癌細胞株做進一步分析。除了IGFBP-5外,其他的基因均在各細胞株中有相當程度的表現,且細胞株間差異不大。然而,IGFBP-5mRNA和蛋白質在八個鱗狀上皮癌細胞株中,只在一個細胞株,SCC25中測得到。進一步發現,IGFBP-5蛋白質主要表現在人類正常口腔上皮組織開始分化的棘狀細胞層,以及顆粒細胞層,在口腔鱗狀細胞癌組織IGFBP-5蛋白質表現量則明顯降低或偵測不到 (P=0.0013paired t -test)。若刺激SCC25及培養之正常口腔上皮細胞(Normal Human Oral Keratinocyte; NHOK)在培養環境中分化,可觀察到IGFBP-5蛋白質的表現受到不同分化狀態的調控。此外,菸草內的一項致癌物B[a]P,會抑制NHOK細胞內IGFBP-5 mRNA及蛋白質表現。因此,IGFBP-5在口腔癌化及上皮細胞分化過程中可能扮演了重要的角色。

   
 

Oral cancer is the fifth most common malignancy of the male population in Taiwan and 90% of that are oral squamous cell carcinomas (OSCCs). Most of the OSCCs are associated with betel quid chewing and smoking. Ingredients in betel quid and tobacco might directly or indirectly change the gene expression profile leading to tumor formation. To identify molecular events that are involved in the pathogenesis of OSCC, genes differentially expressed in OSCC and matched non-cancerous tissues were analyzed using a PCR-based cDNA subtraction method. Six of the clones, CL100, BRCA2, ST13, C/EBP, IGFBP-rP1 and IGFBP-5, were selected from OSCC-down-regulating pool and subjected to semi-quantitative RT-PCR analyses in eight squamous cell carcinoma (SCC) cell lines. Except for IGFBP-5, all genes tested were expressed in these SCC cell lines in a similaar level. IGFBP5 transcript was only detectable in a cell line, SCC25. Immunohoistochemical study revealed a strong cytoplasmic immunoreactivity of IGFBP-5 in the stratum spinosum and stratum granulosum of most normal epithelium. Complete loss or remarkable reduction of IGFBP-5 immunoreactivity was detected in OSCC analyzed (P = 0.001, paired t-test). Induction of differentiation in SCC25 and normal human oral keratinocytes (NHOK) modulates the expression level of IGFBP-5. In addition, employment of a carcinogen in tobacco, B[a]P, down-regulates the levels of IGFBP-5 mRNA and protein. These evidences suggested that IGFBP-5 might play important roles in oral carcinogenesis and differentiation of oral keratinocytes.