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

Overexpression of acidic and basic fibroblast growth factors in human pancreatic cancer correlates with advanced tumor stage.
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DOI:
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发表时间:
1993-11
期刊:
影响因子:
11.2
通讯作者:
Y. Yamanaka;H. Friess;M. Büchler;H. Beger;E. Uchida;M. Onda;M. Kobrin;M. Korc
Y. Yamanaka;H. Friess;M. Büchler;H. Beger;E. Uchida;M. Onda;M. Kobrin;M. Korc
中科院分区:
医学1区
文献类型:
--
作者:
Y. Yamanaka;H. Friess;M. Büchler;H. Beger;E. Uchida;M. Onda;M. Kobrin;M. Korc

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酸性成纤维细胞生长因子和碱性成纤维细胞生长因子是可能促进癌细胞增殖的促有丝分裂多肽。在本研究中,我们检测了aFGF和bFGF在人胰腺癌中的表达。对12例胰腺癌组织的总RNA进行Northern印迹分析发现,与正常人胰腺组织相比,分别有12例和10例胰腺癌组织中aFGFm RNA和bFGFm RNA表达水平升高。免疫组织化学染色显示,在许多癌细胞及癌旁萎缩的腺泡和导管中均有aFGF和bFGF的表达,但在周围成纤维细胞中的表达程度较低。通过原位杂交,这两个部分的mRNA与各自的蛋白共存,并在许多癌细胞中大量存在。免疫印迹证实,aFGF和bFGF免疫反应性增强的癌症组织中这两种蛋白的水平都升高。采用免疫组织化学方法检测78例人胰腺癌组织中aFGFs和bFGFs的表达。在47例(60%)和44例(56%)的肿瘤细胞中,aFGF4和bFGF2表达阳性。癌细胞中aFGF或bFGF的表达与晚期肿瘤分期显著相关,bFGF的表达与患者较短的生存期显著相关。这些数据表明,在相当大比例的人胰腺癌细胞中,aFGF和bFGF过度表达,这种过度表达可能有助于疾病的进展。
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.