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酸性和碱性成纤维细胞生长因子在人胰腺癌中的过表达与肿瘤晚期相关。

Overexpression of acidic and basic fibroblast growth factors in human pancreatic cancer correlates with advanced tumor stage.

作者信息

Yamanaka Y, Friess H, Buchler M, Beger H G, Uchida E, Onda M, Kobrin M S, Korc M

机构信息

Department of Medicine, University of California, Irvine 92717.

出版信息

Cancer Res. 1993 Nov 1;53(21):5289-96.

PMID:7693336
Abstract

Acidic fibroblast growth factor (aFGF) and basic FGF (bFGF) are mitogenic polypeptides that may contribute to cancer cell proliferation. In the present study we examined aFGF and bFGF expression in human pancreatic cancer. Northern blot analysis of total RNA isolated from 12 pancreatic cancers revealed elevated aFGF and bFGF mRNA levels in 12 and 10 samples, respectively, by comparison with the normal human pancreas. Immunostaining demonstrated the presence of aFGF and bFGF in many cancer cells and in the atrophic acini and ducts adjacent to the cancer cells, but to a much lesser extent in the surrounding fibroblasts. By in situ hybridization, both mRNA moieties colocalized with their respective proteins and were abundant in many cancer cells. Immunoblotting confirmed that cancer tissues with increased aFGF and bFGF immunoreactivity contained elevated levels of both proteins. To determine the significance of aFGF and bFGF expression in the pancreatic cancer cells, immunohistochemical analysis of 78 human pancreatic carcinomas was performed. aFGF and bFGF immunoreactivity was present in the cancer cells in 47 (60%) and 44 (56%) of the tumors, respectively. There was a significant correlation between the presence of either aFGF or bFGF in the cancer cells and advanced tumor stage, and the presence of bFGF and shorter patient survival. These data suggest that aFGF and bFGF are overexpressed in a significant proportion of human pancreatic carcinoma cells and that this overexpression may contribute to disease progression.

摘要

酸性成纤维细胞生长因子(aFGF)和碱性成纤维细胞生长因子(bFGF)是促有丝分裂多肽,可能促进癌细胞增殖。在本研究中,我们检测了人胰腺癌中aFGF和bFGF的表达。对从12例胰腺癌中分离的总RNA进行Northern印迹分析显示,与正常人类胰腺相比,分别在12个和10个样本中aFGF和bFGF的mRNA水平升高。免疫染色显示许多癌细胞以及与癌细胞相邻的萎缩腺泡和导管中存在aFGF和bFGF,但在周围成纤维细胞中的表达程度要低得多。通过原位杂交,两种mRNA部分与其各自的蛋白质共定位,并且在许多癌细胞中含量丰富。免疫印迹证实,aFGF和bFGF免疫反应性增加的癌组织中两种蛋白质的水平均升高。为了确定aFGF和bFGF在胰腺癌细胞中表达的意义,对78例人胰腺癌进行了免疫组织化学分析。在47例(60%)和44例(56%)肿瘤的癌细胞中分别存在aFGF和bFGF免疫反应性。癌细胞中存在aFGF或bFGF与肿瘤晚期之间存在显著相关性,并且存在bFGF与患者生存期较短相关。这些数据表明,aFGF和bFGF在相当比例的人胰腺癌细胞中过表达,并且这种过表达可能促进疾病进展。

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