ENHANCED EXPRESSION OF TRANSFORMING GROWTH-FACTOR-BETA ISOFORMS IN PANCREATIC-CANCER CORRELATES WITH DECREASED SURVIVAL
ENHANCED EXPRESSION OF TRANSFORMING GROWTH-FACTOR-BETA ISOFORMS IN PANCREATIC-CANCER CORRELATES WITH DECREASED SURVIVAL
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DOI：
10.1016/0016-5085(93)91084-u
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发表时间：
1993-12-01
期刊：
影响因子：
29.4
通讯作者：
KORC, M
中科院分区：
文献类型：
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作者：
FRIESS, H;YAMANAKA, Y;KORC, M
背景：转化生长因子βs（transforminggrowthfactor βs，TGF-βs）是一类具有抑制或刺激细胞增殖作用的双功能多肽生长因子。TGF-β表达和功能的扰动可能导致细胞生长的负约束的丧失。方法：应用免疫组化、北方印迹和原位杂交技术检测60例胰腺癌组织中TGF-β亚型的分布。结果：免疫组化结果显示TGF-β1（47%）、TGF-β2（42%）和TGF-β3（40%）在胰腺癌细胞中的表达。TGF-β2的表达与肿瘤分期有关（P< 0.05）。此外，肿瘤中TGF-βs的缺失与术后生存期延长之间存在显著相关性。北方杂交结果显示，与正常胰腺组织相比，胰腺癌组织中TGF-β1、TGF-β2和TGF-β3的mRNA水平分别增加了11倍（P<0.001）、7倍（P < 0.05）和9倍（P< 0.001）。结论：胰腺癌组织中TGF-β亚型表达增加，TGF-β mRNA表达增强，提示胰腺癌细胞中TGF-βs的存在可能与疾病进展有关。
Background:Transforming growth factor βs (TGF-βs) constitute a family of bifunctional polypeptide growth factors that either inhibit or stimulate cell proliferation. Perturbations in TGF-β expression and function may lead to loss of negative constraints on cell growth. In this study, we examined TGF-β expression in human pancreatic cancer.Methods:The distribution of TGF-β isoforms in 60 human pancreatic cancers was examined using immunohistochemical, Northern blot, and in situ hybridization techniques.Results:Immunohistochemical analysis showed the presence of TGF-β1 (47% of tumors), TGF-β2 (42% of tumors), and TGF-β3 (40% of tumors) in the cancer cells. The presence of TGF-β2 was associated with advanced tumor stage (P< 0.05). Furthermore, there was a significant correlation between the absence of TGF-βs in the tumors and longer postoperative survival. Northern blot analysis indicated that, by comparison with the normal pancreas, pancreatic adenocarcinomas showed 11- (P< 0.001), 7- (P< 0.05), and 9-fold (P< 0.001) increases in the messenger RNA (mRNA) levels encoding TGF-β1, TGF-β2, and TGF-β3, respectively. By in situ hybridization, these mRNA moieties colocalized with their respective proteins in the cancer cells.Conclusions:These findings show that human pancreatic cancers show increased levels of TGF-β isoforms and enhanced TGF-β mRNA expression and suggest that the presence of TGF-βs in pancreatic cancer cells may contribute to disease progression.