Tuck A B, Park M, Sterns E E, Boag A, Elliott B E
Department of Pathology, Kingston General Hospital, Ontario, Canada.
Am J Pathol. 1996 Jan;148(1):225-32.
Expression of hepatocyte growth factor (HGF) and HGF receptor (HGFR, product of the met proto-oncogene) mRNA were examined by nonisotopic in situ hybridization in a spectrum of benign and malignant human breast tissues. mRNA for both HGFR and HGF was detected in benign ductal epithelium. Epithelial expression of HGF mRNA was particularly intense in regions of ductal epithelial hyperplasia. Positive expression of HGF (but not HGFR) mRNA was also found in adipocytes, endothelial cells, and to varying degrees in stromal fibroblasts. In 12 of 12 cases of ductal carcinoma in situ and infiltrating ductal carcinoma, carcinoma cells showed a heterogeneous pattern of expression for both HGFR and HGF mRNA. In infiltrating ductal carcinomas, intense expression of HGFR mRNA was not restricted to ductular structures but as also seen in non-duct-forming carcinoma cells. The same zones of the tumors (most commonly at the advancing margins) that expressed strongly HGFR mRNA often were also strongly positive for HGF mRNA, suggesting a possible autocrine effect. The expression pattern of HGFR protein in 25 cases including the same series of tissues used for in situ hybridization analysis was similar to that of HGFR mRNA, as determined by an immunoperoxidase technique. The finding that HGFR is expressed by both benign and malignant epithelium, and its not restricted to duct-forming structures, suggests that, although the potential for HGF/HGFR binding is maintained in malignancy, the response to ligand binding at the level of the receptor or the cellular response to receptor activation may change at some point during progression.
采用非同位素原位杂交技术，检测了一系列人乳腺良恶性组织中肝细胞生长因子（HGF）及其受体（HGFR，原癌基因met的产物）mRNA的表达情况。在良性导管上皮中检测到了HGFR和HGF的mRNA。HGF mRNA的上皮表达在导管上皮增生区域尤为强烈。在脂肪细胞、内皮细胞以及不同程度的基质成纤维细胞中也发现了HGF（而非HGFR）mRNA的阳性表达。在12例原位导管癌和浸润性导管癌中，癌细胞均呈现出HGFR和HGF mRNA的异质性表达模式。在浸润性导管癌中，HGFR mRNA的强烈表达不仅局限于导管结构，在非导管形成的癌细胞中也可见。肿瘤中表达强烈HGFR mRNA的相同区域（最常见于进展边缘）通常HGF mRNA也呈强阳性，提示可能存在自分泌效应。通过免疫过氧化物酶技术检测，包括用于原位杂交分析的相同系列组织在内的25例组织中HGFR蛋白的表达模式与HGFR mRNA相似。HGFR在良性和恶性上皮中均有表达且不限于导管形成结构，这一发现表明，尽管在恶性肿瘤中仍存在HGF/HGFR结合的潜力，但在肿瘤进展过程中的某个阶段，受体水平对配体结合的反应或细胞对受体激活的反应可能会发生变化。
