PPP2R1B基因在人類子宮頸癌之突變分析; Mutation Analysis of the PPP2R1B Gene in Cervical Cancer

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Title:	PPP2R1B基因在人類子宮頸癌之突變分析;Mutation Analysis of the PPP2R1B Gene in Cervical Cancer
Authors:	葉聯舜;Lian-Shung Yeh
Contributors:	中國醫藥學院醫學研究所
Keywords:	蛋白去磷酸;2A;異配子喪失;絲胺酸-色胺磷酸;子宮頸癌;protein phosphatase 2A;loss of heterozygosity;LOH;serine-threonine phosphatase;cervical cancer
Date:	1999
Issue Date:	2009-12-02 14:11:08 (UTC+8)
Abstract:	中文摘要背景 PPP2R1B基因是蛋白去磷酸■;2A (protein phosphatase 2A: PP2A)的亞型。PP2A涉及細胞週期的控制及一些成長激素的訊息傳導。PPP2R1B基因位於人體第11染色體長臂第22至24區 (11q22-24) 之內，此區域在許多腫瘤裡常有異配子喪失現象(loss of heterozygosity; LOH)。LOH常表示該區域具有抑癌基因，因為一般細胞的癌化過程，是由於許多種的基因發生變異，而導致生長失控的現象。這些基因的變化，包括了致癌基因的活化及抑癌基因的不活化。所以PPP2R1B被認為是個抑癌因子，而此基因的變化與11q的喪失可能有直接關係。最近，PPP2R1B基因突變已在原發性肺癌、直腸癌及源自肺癌細胞的腫瘤細胞株中發現。本研究乃探討在子宮頸癌裡PPP2R1B的基因變化。由基因發生變化的情形，有助於辨識癌化過程，而且也可判定PPP2R1B基因的LOH現象與子宮頸癌病變過程之關聯，並提供我們治療與預防的方針。方法蒐集24例子宮頸癌之腫瘤組織及鄰近之正常組織加以研究。先用反轉錄-聚合■;鏈反應(reverse transcriptase-polymerase chain reaction; RT-PCR)來篩檢此基因的變化，再用直接定序(direct sequencing)來分析各種不同的突變。結果 24件子宮頸癌之組織有5件檢出有aberrant transcripts，其配對之正常子宮頸組織則有8件檢出有aberrant transcripts。結論從本研究之結果顯示，在子宮頸癌組織及鄰近之正常子宮頸組織皆可檢出有aberrant transcripts。在子宮頸癌組織PPP2R1B基因的突變，並不同於肺癌及大腸癌PPP2R1B基因之突變。密碼子codon 66 CTA66->CTG之取代轉變(transition)，可能是一種非病理性的多形性變化。; 英文摘要 Abstract The PPP2R1B gene encodes the b isoform of the A subunit of the serine/threonine protein phosphatase 2A (PP2A). PP2A holoenzyme plays a critical role in cell-cycle control and growth-factor signaling. The PPP2R1B gene is located on human chromosome 11q22-24 where loss of heterozygosity (LOH) was frequently observed in many carcinomas. LOH is a very important sign for analyzing the deletion of tumor suppressor genes, which lead to the development of a variety of human malignancies. Hence, PPP2R1B is a putative tumor suppressor gene and its alterations may be related to tumor development. Recently, the PPP2R1B gene somatic alterations were found in primary lung tumors, lung-derived cell line and primary colon tumors. In this study, we used nested RT-PCR and direct sequencing to analyzing 24 cases of cervical cancers and paired non-cancerous near-by tissues. The results showed that aberrant transcripts were found 5/24 cases of cancerous tissues, and 8/24 cases of non-cancerous tissues. We suggest that these aberrant transcripts play no role in the carcinogenesis of cervical cancer, and we also sequenced the whole cDNA of RT-PCR product of PPP2R1B, no point mutation or small-bases change in these 24 cervical cancers. We suggest that PPP2R1B may not play a role in the development of cervical cancer.
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