Maurer C A, Friess H, Kretschmann B, Zimmermann A, Stauffer A, Baer H U, Korc M, Büchler M W
Department of Visceral and Transplantation Surgery, University of Berne, Inselpital, Switzerland.
Hum Pathol. 1998 Aug;29(8):771-7. doi: 10.1016/s0046-8177(98)90444-0.
ErbB3 is a transmembrane signaling molecule that shares close structural homology with epidermal growth factor receptor (EGFR), erbB2, and erbB4. They have all been implicated in cell transformation and tumor pathogenesis, but very little is known about the role of erbB3 in normal colon and colorectal cancer. Therefore, in the current study, we determined whether erbB3 is found in normal human colon and whether its expression is altered in colorectal cancer. Because of some evidence that erbB3 might interact with erbB2 and EGFR, respectively, by heterodimerization, we also included erbB2 and EGFR analysis with special regard to coexpression. The study was performed on 35 patients operated on for colorectal carcinoma. The normal human colon showed weak erbB3 and erbB2 immunostaining, predominantly in surface epithelial cells. EGFR immunoreactivity in normal colon varied from weak to strong. In contrast, in 31 of 35 (89%) and in 29 of 35 (83%) colonic cancers, moderate to strong immunoreactivity for erbB3 and erbB2, respectively, was present in most epithelial cancer cells. A concomitant erbB3 and erbB2 immunostaining advantage could be found in 77% of cancerous tissues in comparison with the normal colon. No difference in EGFR immunostaining was evident between normal colon and cancer. Northern blot analysis showed an increase in erbB3 and erbB2 mRNA levels in 64% of cancers in comparison with normal colon samples. By densitometry, 2.3-fold and a 1.5-fold significant increases in erbB3 and erbB2 mRNA levels, respectively, were calculated in the cancerous tissues. Eighty-five percent of cancers with erbB3 mRNA overexpression showed an increase in erbB2 mRNA. Southern blot analysis did not indicate any gene amplification or rearrangement responsible for erbB2 or erbB3 overexpression. EGFR, however, was decreased in cancer on mRNA level. These findings indicate that erbB2 and erbB3, but not EGFR, may contribute to tumor growth and disease progression in colon cancer. The correlation between increased erbB2 and erbB3 expression in both Northern blots and immunohistochemical analysis suggests a co-overexpression of erbB2 and erbB3 and might support the hypothesis that these two growth factor receptors act together by heterodimer formation.
ErbB3是一种跨膜信号分子，与表皮生长因子受体（EGFR）、erbB2和erbB4在结构上具有高度同源性。它们均与细胞转化和肿瘤发病机制有关，但关于erbB3在正常结肠和结直肠癌中的作用却知之甚少。因此，在本研究中，我们检测了erbB3在正常人类结肠中的表达情况以及其在结直肠癌中表达是否改变。鉴于有证据表明erbB3可能分别通过异源二聚化与erbB2和EGFR相互作用，我们还特别对erbB2和EGFR进行了共表达分析。本研究对35例接受结直肠癌手术的患者进行。正常人类结肠显示erbB3和erbB2免疫染色较弱，主要见于表面上皮细胞。正常结肠中EGFR免疫反应性强弱不一。相比之下，在35例结肠癌患者中的31例（89%）和29例（83%）中，大多数上皮癌细胞中erbB3和erbB2分别呈现中度至强免疫反应性。与正常结肠相比，77%的癌组织中可发现erbB3和erbB2免疫染色同时增强。正常结肠和癌组织中EGFR免疫染色无明显差异。Northern印迹分析显示，与正常结肠样本相比，64%的癌组织中erbB3和erbB2 mRNA水平升高。通过光密度测定法，癌组织中erbB3和erbB2 mRNA水平分别显著增加了2.3倍和1.5倍。85%的erbB3 mRNA过表达的癌组织中erbB2 mRNA也增加。Southern印迹分析未显示任何导致erbB2或erbB3过表达的基因扩增或重排。然而，癌组织中EGFR mRNA水平降低。这些发现表明，erbB2和erbB3而非EGFR可能在结肠癌的肿瘤生长和疾病进展中发挥作用。Northern印迹分析和免疫组织化学分析中erbB2和erbB3表达增加之间的相关性表明erbB2和erbB3共同过表达，可能支持这两种生长因子受体通过形成异源二聚体共同发挥作用这一假说。
