Bax而非Bcl-2影响人类胰腺癌的预后。
bax, but not bcl-2, influences the prognosis of human pancreatic cancer.
作者信息
Friess H, Lu Z, Graber H U, Zimmermann A, Adler G, Korc M, Schmid R M, Büchler M W
机构信息
Department of Visceral and Transplantation Surgery, University of Bern, Inselspital, Switzerland.
出版信息
Gut. 1998 Sep;43(3):414-21. doi: 10.1136/gut.43.3.414.
BACKGROUND
bcl-2 and bax belong to the bcl-2-related gene family, which marks a new class of genes that influence apoptosis. The bcl-2 oncogene acts as a broad antiapoptotic factor and extends both normal and tumour cell survival. In contrast, the bax gene is a promoter of apoptosis.
AIMS
To analyse the expression of bcl-2 and bax in pancreatic cancer and correlate the results with clinical parameters.
PATIENTS
Pancreatic cancer tissue samples were obtained from 28 female and 32 male patients (median age 63, range 43-79 years) having surgery for pancreatic cancer. Normal pancreatic tissues obtained from 18 previously healthy organ donors served as controls.
METHODS
The levels of bcl-2 and bax mRNA expression were analysed by northern blot and the exact site of mRNA transcription was determined by in situ hybridisation. The presence of the corresponding proteins was determined by immunohistochemistry.
RESULTS
Northern blot analysis indicated that, in comparison with the normal pancreas, bcl-2 mRNA was overexpressed in 30% and bax mRNA in 61% of the pancreatic cancer samples. Concomitant overexpression of bcl-2 and bax was present in 26% of the cancer samples. Pancreatic adenocarcinomas exhibited 3.7-fold and 5.4-fold increases (p < 0.001) in bcl-2 and bax mRNA levels respectively. In situ hybridisation showed that both bcl-2 and bax mRNA were expressed in the cancer cells. Immunohistochemical analysis showed positive Bcl-2 and Bax immunostaining in 28 and 83% of the cancer samples respectively. In multivariate analysis (Cox regression model), bax expression was found to be a strong indicator of survival (p < 0.001). Patients whose tumours exhibited Bax immunostaining lived significantly longer (12 months) than those whose tumours were Bax negative (five months) (p < 0.039). In contrast, no relation was found between Bcl-2 and survival time.
CONCLUSIONS
The data indicate that genes that are involved in the regulation of apoptosis are upregulated in human pancreatic cancer cells. Prolonged survival times in patients in whom apoptosis promoting factors are upregulated indicate that apoptotic pathways are of biological significance in pancreatic cancer.
背景
bcl-2和bax属于bcl-2相关基因家族，这是一类影响细胞凋亡的新基因。bcl-2癌基因作为一种广泛的抗凋亡因子，可延长正常细胞和肿瘤细胞的存活时间。相比之下，bax基因是细胞凋亡的促进因子。
目的
分析bcl-2和bax在胰腺癌中的表达情况，并将结果与临床参数相关联。
患者
从28例女性和32例男性胰腺癌患者（中位年龄63岁，范围43 - 79岁）中获取胰腺癌组织样本，这些患者均接受了胰腺癌手术。从18名先前健康的器官供体获取的正常胰腺组织作为对照。
方法
通过Northern印迹分析bcl-2和bax mRNA表达水平，并通过原位杂交确定mRNA转录的确切位点。通过免疫组织化学确定相应蛋白质的存在。
结果
Northern印迹分析表明，与正常胰腺相比，30%的胰腺癌样本中bcl-2 mRNA过表达，61%的样本中bax mRNA过表达。26%的癌样本中bcl-2和bax同时过表达。胰腺腺癌中bcl-2和bax mRNA水平分别升高3.7倍和5.4倍（p < 0.001）。原位杂交显示癌细胞中bcl-2和bax mRNA均有表达。免疫组织化学分析显示，分别有28%和83%的癌样本中Bcl-2和Bax免疫染色呈阳性。在多变量分析（Cox回归模型）中，发现bax表达是生存的有力指标（p < 0.001）。肿瘤表现为Bax免疫染色阳性的患者生存时间明显长于（12个月）肿瘤为Bax阴性的患者（5个月）（p < 0.039）。相比之下，未发现Bcl-2与生存时间之间存在关联。
结论
数据表明参与细胞凋亡调控的基因在人胰腺癌细胞中上调。凋亡促进因子上调的患者生存时间延长表明凋亡途径在胰腺癌中具有生物学意义。
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