成纤维细胞生长因子-1 (FGF-1)和FGF受体-1 (FGFR-1)在人乳腺癌中的表达和定位

Norio Yoshimura , Hajime Sano , Akira Hashiramoto , Ryoji Yamada , Hiroo Nakajima , Motoharu Kondo , Takahiro Oka
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引用次数: 72

摘要

成纤维细胞生长因子-1 (FGF-1)是血管生成的诱导剂,新血管的生长。应用Western blot和免疫组织化学方法研究了乳腺癌患者乳腺组织中FGF-1(酸性FGF)和FGF受体(FGFR)-1的表达和定位。本研究采用亲和纯化的FGF-1抗体,该抗体与FGF-2(碱性FGF)无交叉反应性。Western blot分析显示,所有乳腺癌样本中都存在FGF-1蛋白,但良性肿瘤如乳腺病和纤维腺瘤中不存在FGF-1蛋白。为了评估FGF-1在癌组织中的定位,采用特异性抗体进行免疫染色。所有乳腺癌样本均显示出明显的FGF-1抗体染色。肿瘤细胞中免疫反应性FGF-1多肽的程度和强度在统计学上远远大于纤维腺瘤或乳腺病变细胞。用正常兔血清或重组FGF-1多肽吸附的抗FGF-1抗体进行对照免疫染色均为完全阴性。与FGF-1相比,Western blot分析显示,FGFR-1蛋白存在于乳腺癌和良性肿瘤的所有样本中。通过免疫组化分析,FGFR-1在乳腺癌细胞中的表达增强。良性肿瘤细胞或间质细胞显示微弱的FGFR-1表达。这些结果表明,乳腺癌细胞不仅可以产生FGFR-1,还可以表达FGFR-1,并且FGF-1可能通过旁分泌和自分泌机制在乳腺癌细胞增殖中发挥作用。
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The Expression and Localization of Fibroblast Growth Factor-1 (FGF-1) and FGF Receptor-1 (FGFR-1) in Human Breast Cancer

Fibroblast growth factor-1 (FGF-1) is an inducer of angiogenesis, the growth of new blood vessels. The expression and localization of FGF-1 (acidic FGF) and FGF receptor (FGFR)-1 in mammary tissues from patients with breast cancer was investigated using Western blot analysis and immunohistochemistry. The affinity-purified FGF-1 antibody which did not have cross-reactivity to FGF-2 (basic FGF) was used in this study. Western blot analysis demonstrated the presence of FGF-1 protein in all of the samples from breast cancer, but not benign tumors such as mastopathy and fibroadenoma. To assess the localization of FGF-1 in cancer tissues, immunostaining with specific antibody was performed. All samples from breast cancer displayed significantly intense staining with FGF-1 antibody. The extent and intensity of immunoreactive FGF-1 polypeptides in cancer cells was statistically much greater than those of cells from fibroademoma or mastopathy. Control immunostaining with normal rabbit serum or anti-FGF-1 antibody adsorbed with the recombinant FGF-1 polypeptide was completely negative. In contrast to FGF-1, Western blot analysis demonstrated the presence of FGFR-1 protein in all of the samples from breast cancer and benign tumors. By immunohistochemical analysis, the enhanced expression of FGFR-1 was observed in breast cancer cells. Benign tumor cells or interstitial cells displayed a faint expression of FGFR-1. These results demonstrated that breast cancer cells not only generated FGF-1, but also expressed FGFR-1, and FGF-1 might play a role in the proliferation of breast cancer cells not only by paracrine but also by autocrine mechanism.

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