Expression of basic fibroblast growth factor, FGFR1 and FGFR2 in normal and malignant human breast, and comparison with other normal tissues.

Expression of basic fibroblast growth factor, FGFR1 and FGFR2 in normal and malignant human breast, and comparison with other normal tissues.
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DOI:
10.1038/bjc.1992.256
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发表时间:
1992-08
影响因子:
8.8
通讯作者:
Coombes, R C
Coombes, R C
中科院分区:
医学1区
文献类型:
--
作者:
Luqmani, Y A;Graham, M;Coombes, R C

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使用聚合酶链反应检测碱性成纤维细胞生长因子(bFGF)及其两种受体FGFR 1和FGFR 2的表达,并通过与普遍存在的甘油醛磷酸脱氢酶转录物共扩增后获得的产物的相对量进行比较来定量。在绝大多数癌症和非恶性乳腺活检以及其他几种正常人体组织样本中发现了不同的水平。癌组织中bFGF的表达明显减少(P <0.0001)。类似地,FGFR 2产物在癌组织中也少得多(P = 0.0078),FGFR 1也是如此(P = 0.002)。雌激素受体阳性的乳腺癌组织中FGFR 1的表达水平明显高于雌激素受体阳性的乳腺癌组织(P <0.06)。不同编码区的扩增显示FGFR 1 RNA变体形式的证据。癌症似乎具有与第三免疫球蛋白样结构域和酪氨酸激酶结构域之间的区域相对应的显著更大比例的PCR产物(P = 0.046)。在乳腺细胞系中观察到差异表达,bFGF在正常来源的HBL 100、HBR SV1.6.1和184 A1中,但在ZR-75-1、MCF-7、T47 D和MDA-MB-231中很少或没有。FGFR 1存在于大多数这些中,但FGFR 2不存在于T47 D、MDA-MB-231和HBL 100中。ZR-75-1细胞具有明显优势的FGFR 1变体缺乏部分编码序列。异常的受体加工可能提供有关FGF的作用及其在恶性肿瘤中的潜在参与的线索。
The expression of basic fibroblast growth factor (bFGF) and two of its receptors, FGFR1 and FGFR2, was detected using the polymerase chain reaction, and quantified by comparison to the relative amount of product obtained following co-amplification of the ubiquitous glyceraldehyde phosphate dehydrogenase transcript. Varying levels were found in the vast majority of both cancer and non-malignant breast biopsies as well as in samples of several other normal human tissues. Significantly less bFGF was present in cancers (P less than 0.0001). Similarly, FGFR2 product was also much less in cancer tissues (P = 0.0078), as was FGFR1 (P = 0.002). FGFR1 levels in cancers tended to be higher in those which were oestrogen receptor positive (P less than 0.06). Amplification of different coding regions showed evidence of variant forms of FGFR1 RNA. Cancers appeared to have a significantly greater proportion of PCR product corresponding to the region between the third immunoglobulin like domain and the tyrosine kinase domain (P = 0.046). Differential expression was observed in breast cell lines, with bFGF in the normal derived HBL100, HBR SV1.6.1 and 184A1 but little or none in ZR-75-1, MCF-7, T47D and MDA-MB-231. FGFR1 was present in most of these but FGFR2 was absent from T47D, MDA-MB-231 and HBL100. ZR-75-1 cells had a marked preponderance of FGFR1 variants lacking part of the coding sequence. Aberrant receptor processing may provide clues concerning the role of FGF's and their potential involvement in malignancy.