The location of acidic fibroblast growth factor in the breast is dependent on the activity of proteases present in breast cancer tissue.

The location of acidic fibroblast growth factor in the breast is dependent on the activity of proteases present in breast cancer tissue.
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DOI:
10.1038/bjc.1997.277
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发表时间:
1997
影响因子:
8.8
通讯作者:
Gomm JJ
Gomm JJ
中科院分区:
医学1区
文献类型:
--
作者:
Coope RC;Browne PJ;Yiangou C;Bansal GS;Walters J;Groome N;Shousha S;Johnston CL;Coombes RC;Gomm JJ

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酸性成纤维细胞生长因子(FGF1)和它的两个受体,FGFR1和FGFR4,定位在正常,良性和恶性人乳腺组织的冷冻切片免疫组织化学。未经预处理,FGF1染色主要见于正常上皮细胞。然而,聚合酶链反应(PCR)分析和免疫印迹分离的正常上皮细胞和肌上皮细胞显示FGF1 mRNA和蛋白质存在于这两种细胞类型。冷冻切片在37 ℃磷酸盐缓冲液中孵育后,肌上皮细胞和癌细胞附近的基底膜也显示FGF1染色。用蛋白酶抑制剂处理表明,这种效果是由于内源性蛋白酶的活性。相反,发现FGF1染色仅在蛋白酶抑制剂存在下与恶性细胞相邻的基质相关。FGFR1和FGFR4免疫染色定位于正常和恶性上皮细胞,并且在较小程度上定位于肌上皮细胞。正常和癌症样品之间FGF受体的染色强度没有差异。正常和恶性组织之间的FGF 1的位置的变化和储存的FGF 1的内源性蛋白酶的作用的敏感性提高了FGF 1在正常和恶性人类乳腺中的自分泌和旁分泌作用的可能性。
Acidic fibroblast growth factor (FGF1) and two of its receptors, FGFR1 and FGFR4, were localized in cryostat sections of normal, benign and malignant human breast tissue by immunohistochemistry. Without pretreatment, FGF1 staining was mainly seen in normal epithelial cells. However, polymerase chain reaction (PCR) analysis and immunoblotting of isolated normal epithelial and myoepithelial cells showed FGF1 mRNA and protein to be present in both cell types. Following incubation of frozen sections at 37 degrees C in phosphate-buffered saline, FGF1 staining was also revealed in myoepithelial cells and basement membrane adjacent to carcinoma cells. Treatment with protease inhibitors demonstrated that this effect was due to the activity of an endogenous protease. In contrast, FGF1 staining was found to be associated with the stroma adjacent to malignant cells only in the presence of protease inhibitors. FGFR1 and FGFR4 immunostaining was localized to both normal and malignant epithelial cells and to a lesser extent to myoepithelial cells. There was no difference in the staining intensity for the FGF receptors between normal and cancer samples. The change in location of FGF1 between normal and malignant tissues and the sensitivity of stored FGF1 to the action of endogenous proteases raises the possibility of both autocrine and paracrine roles for FGF1 in the normal and malignant human breast.