原癌基因c-jun与槟榔、口腔鳞状上皮癌的关系研究
摘要
台湾地区口腔癌的流行率，已然跃居十大癌症死亡率的第七位。若单就男性而言，其死亡率及发生率均位居第五位。根据台湾地区卫生署2001年度癌症登记报告指出，口腔癌的死亡率年增加达14.20％，为所有恶性肿瘤死亡率增幅最大者，为当年度癌症平均死亡率的二倍，可见问题之严重。从流行病学研究指出，口腔癌的发生与嚼食槟榔有密切关系。最近分子生物学的研究发现，癌症的发生是由于细胞基因发生改变。这些基因损伤往往发生于致癌基因或抑癌基因上，这些损伤的基因没有修复，不断地积累积将引发肿瘤。在台湾槟榔及其内含物萃取物(Areca nut extract, ANE)被认为是造成口腔细胞变性致癌的重要物质，槟榔萃取物(ANE)可以引发很多的口腔细胞致癌基因发生过度活化并产生突变，进而变成口腔癌的局面。
本研究以槟榔萃取物(ANE)及槟榔主成份槟榔碱(arecoline)刺激口腔黏膜纤维细胞(oral mucosal fibroblast, OMF)，观察其中原癌基因c-junmRNA的表达状况，以便观察槟榔成分是否会诱导c-jun mRNA的过度表现。结果发现，c-jun mRNA受到200μg／ml ANE或10μg／ml槟榔碱的刺激后约一小时，便会约有比对照组增加三倍的c-jun mRNA表达量增加，而在六小时之后回到原始的表达程度，这样结果类似以对照组100 ng／ml TPA处理OMF细胞后的情况一样。以上的事实说明，槟榔萃取物(ANE)及槟榔碱可以诱导OMF中的c-jun mRNA致癌基因的高度比正常的情况高出三倍的量表达，因为持续的c-jun mRNA表达可以造成动物纤维细胞的癌化，因此我们推论槟榔萃取物及槟榔素刺激OMF其细胞c-jun mRNA会产生较高的表现，可能是台湾地区嚼食槟榔口腔癌致癌的机转之一。
In Taiwan, the prevalence of oral cancer has been ranked the seventh to ten leading cancers resulting in mortality. Individually among males, oral cancer is the fifth leading cancer both in incidence and mortality. According to a report of cancer registration conducted by Department of health in 2001, the annual mortality of oral SCC (squamous cell carcinoma) in Taiwan has greatly increased up to 14.20%, which was the highest in all carcinomas and twice as great as the average mortality of the year.
Numerous epidemiological studies have found and association between the incidence of oral cancers and betel nut chewing. Recent studies in molecular biology have found that the incidence of various cancers resulted from genetic changes. These gene damages were thought to be prevalent in oncogene and tumor suppressor gene. These damaged genes were not repaired and caused the genesis of tumors. Betel nuts and the betel nut extract (ANE) were believed to be the risk factors, which might exacerbate the carcinogenic properties. Other studies have found a significant difference between the ingredients in betel nuts and the incidence of oral cancer in Taiwan, which might induce the over-expression and mutation of oncogene.
The study was designed to use the betel nut extract (ANE) and arecoline to examine the expression of proto-oncogene c-jun mRNA in oral submucous fibroblast (OMF) to determine whether or not the ingredients in extract nuts induce the over-expression of c-jun. The results suggested that the betel nut extract (ANE) and arecoline might induce the over-expression of proto-oncogene c-jun mRNA, which was three times higher compared with that in a normal condition. Since the constant expression of c-jun mRNA may cause carcinogenesis of fibroblasts, our results clearly show that the betel nut extract (ANE) and arecoline induce higher level of expression of proto-oncogene c-jun RNA in oral submucous fibroblast(OMF) may be one the mechanism in the carcinogenesis of oral SCC in Taiwan.
Because of the high invasion and low survival rate in oral cancer, the goal to
本研究以槟榔萃取物(ANE)及槟榔主成份槟榔碱(arecoline)刺激口腔黏膜纤维细胞(oral mucosal fibroblast, OMF)，观察其中原癌基因c-junmRNA的表达状况，以便观察槟榔成分是否会诱导c-jun mRNA的过度表现。结果发现，c-jun mRNA受到200μg／ml ANE或10μg／ml槟榔碱的刺激后约一小时，便会约有比对照组增加三倍的c-jun mRNA表达量增加，而在六小时之后回到原始的表达程度，这样结果类似以对照组100 ng／ml TPA处理OMF细胞后的情况一样。以上的事实说明，槟榔萃取物(ANE)及槟榔碱可以诱导OMF中的c-jun mRNA致癌基因的高度比正常的情况高出三倍的量表达，因为持续的c-jun mRNA表达可以造成动物纤维细胞的癌化，因此我们推论槟榔萃取物及槟榔素刺激OMF其细胞c-jun mRNA会产生较高的表现，可能是台湾地区嚼食槟榔口腔癌致癌的机转之一。
In Taiwan, the prevalence of oral cancer has been ranked the seventh to ten leading cancers resulting in mortality. Individually among males, oral cancer is the fifth leading cancer both in incidence and mortality. According to a report of cancer registration conducted by Department of health in 2001, the annual mortality of oral SCC (squamous cell carcinoma) in Taiwan has greatly increased up to 14.20%, which was the highest in all carcinomas and twice as great as the average mortality of the year.
Numerous epidemiological studies have found and association between the incidence of oral cancers and betel nut chewing. Recent studies in molecular biology have found that the incidence of various cancers resulted from genetic changes. These gene damages were thought to be prevalent in oncogene and tumor suppressor gene. These damaged genes were not repaired and caused the genesis of tumors. Betel nuts and the betel nut extract (ANE) were believed to be the risk factors, which might exacerbate the carcinogenic properties. Other studies have found a significant difference between the ingredients in betel nuts and the incidence of oral cancer in Taiwan, which might induce the over-expression and mutation of oncogene.
The study was designed to use the betel nut extract (ANE) and arecoline to examine the expression of proto-oncogene c-jun mRNA in oral submucous fibroblast (OMF) to determine whether or not the ingredients in extract nuts induce the over-expression of c-jun. The results suggested that the betel nut extract (ANE) and arecoline might induce the over-expression of proto-oncogene c-jun mRNA, which was three times higher compared with that in a normal condition. Since the constant expression of c-jun mRNA may cause carcinogenesis of fibroblasts, our results clearly show that the betel nut extract (ANE) and arecoline induce higher level of expression of proto-oncogene c-jun RNA in oral submucous fibroblast(OMF) may be one the mechanism in the carcinogenesis of oral SCC in Taiwan.
Because of the high invasion and low survival rate in oral cancer, the goal to
引文
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