論文名稱:

終末子酉每活性之表現為口腔鱗狀上皮癌癌化中之早期變異

 

Telomerase activity is an early event in oral carcinogenesis

研究生:

張蓮鈺  Lien-Yu Chang

 

(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

          學年度:

86

          語文別:

中文

          出版年:

87

關鍵字:

牙醫  DENTIST

 

牙醫學  DENTISTRY

 

口腔  ORAL-HEALTH

 

終末子脢  Telomerase

 

終末子脢活性  Telomerase activity

 

癌旁正常組織  Adjacent normal tissues

 

口腔鱗狀上皮癌  Tumorigenesis

 

癌化過程  OSCC

摘要:

終末子酉每(telomerase),為蛋白質與RNA組成的複合物,是培養細胞進入不死期(immortalization)的關鍵性酵素,與癌化過程(tumiorigenesis)中可能出現的不死細胞有關係。終末子酉每活性在大部份的人類腫瘤中發現,但在一般的體細胞中卻偵測不到它的活性。本研究利用非放射線性的終末複序擴大法(TRAP)偵測四種口腔角質細胞,及得自54位病人的81例口腔組織標本。並以digoxigenin標記的反意股hTR(人類終末子酉每複合物中的RNA組成分)探針在52例組織切片(來自28位病人)上做原位雜合反應(in Situhybridization),以期能確切定位出口腔鱗狀上皮癌癌化組織中擁有終末子酉每活性的變異細胞。本研究的結果顯示,終末子酉每活性在85.7%(36/42)的口腔鱗狀上皮癌,66.7%(8/12)的癌前病灶以及22.2%(6/27)的癌旁正常組織中出現;所有3例口腔鱗狀上皮癌癌細胞衍生而來的細胞株都有很強的終末子酉每活性,然而1例正常口腔角質培養細胞中卻未偵測到終末子酉每活性。至於hTR的原住表現則在 85%(23/27)口腔鱗狀上皮癌和 80%(20/25)癌旁正常組織中觀察到。統計分析顯示hTR的表現與腫瘤分化程度有關,但在癌旁正常組織中亦有類似於其配對癌組織中之hTR表現;此外,hTR表現率與終末子酉每活性的出現並不同步。hTR像是一個有組織特異性的穩定分子,可能與細胞的分化或增殖狀態較有關係。我們推論其表現的調節與終末子酉每酵素活性的調控可能沒有直接關係。由於終末子酉每活性出現在大部份 的口腔鱗狀上皮癌及癌前病灶中,而且癌前病灶中的終末子酉每活性表現率亦近似於口腔鱗狀上皮癌,顯示終末子酉每的激活在口腔鱗狀上皮癌癌化過程的早期出現,而且可能發生於由癌 旁正常組織變化到癌前病灶的時期。

   
 

During tumorigenesis, replicative senescence breaks down to yield immortal cells, which can proliferative indefinitely and may facilitate tumor progression. Telomerase, a ribonucleic acid (RNA)-protein complex, is a critical enzyme for maintaining immortal phenotypes. Recently, telomerase activity has been detected in many human cancers, but not in most somatic tissues.  To investigate the role of telomerase in oral carcinogenesis, we assayed telomerase activity in variable oral tissues by a modified, non-radioactive, telomere repeat amplification protocol (TRAP).  Furthermore, using the digoxigenin labeled anti-sense hTR(human telomerase RNA component) probe, we measured the in situ expression of hTR in tissue sections of paired OSCCs and adjacent normal tissues. We found telomerase activity presenting in all 3 cell lines derived from OSCC, but not in the primary culture of normal oral keratinocyte. During oral carcinogenesis, most OSCCs (36/42, 85.7%) and oral premalignant lesions (8/12, 66.7%) possessed telomerase activity.  In addition, 6 of 27(22.2%) adjacent normal tissues also contained weak  telomerase activity. In situ hybridization showed that hTR expressed in almost all OSCCs (23/27, 85%) as well as adjacent normal tissues (20/25,  80%). No increase of the hTR expression that paralleled the increase of telomerase activity was noted during the morphological change from normal to neoplastic cells.  The relationship between the hTR expression  and more advanced tumor grade was remarkable. Our data suggested  that the regulation of telomerase activity may be distinct from the expression of its RNA components. The hTR expression may be regulated by the cellular differentiation or the cellular proliferation. This study highlights that the activation of telomerase activity is a frequent  event in OSCCs and this alteration may occur during the transformation  process of normal oral epithelium to premalignancies.