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碱性成纤维细胞生长因子、FGFR1和FGFR2在正常及恶性人乳腺组织中的表达及其与其他正常组织的比较

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

作者信息

Luqmani Y A, Graham M, Coombes R C

机构信息

Department of Medical Oncology, Charing Cross Hospital Medical School, London, UK.

出版信息

Br J Cancer. 1992 Aug;66(2):273-80. doi: 10.1038/bjc.1992.256.

Abstract

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.

摘要

采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FGFR1和FGFR2的表达,并通过与磷酸甘油醛脱氢酶转录本共扩增后获得的产物相对量进行比较来定量。在绝大多数乳腺癌和非恶性乳腺活检组织以及其他几种正常人体组织样本中均发现了不同水平的表达。癌症组织中bFGF的含量明显较低(P<0.0001)。同样,癌症组织中FGFR2产物也少得多(P = 0.0078),FGFR1也是如此(P = 0.002)。雌激素受体阳性的癌症中FGFR1水平往往较高(P<0.06)。不同编码区的扩增显示出FGFR1 RNA变体形式的证据。癌症似乎有更大比例的PCR产物对应于第三个免疫球蛋白样结构域和酪氨酸激酶结构域之间的区域(P = 0.046)。在乳腺细胞系中观察到差异表达,正常来源的HBL100、HBR SV1.6.1和184A1中有bFGF,但ZR-75-1、MCF-7、T47D和MDA-MB-231中很少或没有。这些细胞系中的大多数都存在FGFR1,但T47D、MDA-MB-231和HBL100中不存在FGFR2。ZR-75-1细胞中存在大量缺乏部分编码序列的FGFR1变体。异常的受体加工可能为FGF的作用及其在恶性肿瘤中的潜在参与提供线索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ed5/1977809/687877649504/brjcancer00060-0054-a.jpg

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