Cancer Research UK Clinical Centre, St James University Hospital, Beckett Street, Leeds LS9 7TF, UK.
Br J Cancer. 2011 Mar 29;104(7):1135-43. doi: 10.1038/bjc.2011.39. Epub 2011 Mar 1.
Therapies targeting ERBB2 have shown success in the clinic. However, response is not determined solely by expression of ERBB2. Levels of ERBB3, its preferred heterodimerisation partner and ERBB ligands may also have a role.
We measured NRG1 expression by real-time quantitative RT-PCR and ERBB receptors by western blotting and immunohistochemistry in bladder tumours and cell lines.
NRG1α and NRG1β showed significant coordinate expression. NRG1β was upregulated in 78% of cell lines. In tumours, there was a greater range of expression with a trend towards increased NRG1α with higher stage and grade. Increased expression of ERBB proteins was detected in 15% (EGFR), 20% (ERBB2), 41% (ERBB3) and 0% (ERBB4) of cell lines. High EGFR expression was detected in 28% of tumours, associated with grade and stage (P=0.05; P=0.04). Moderate or high expression of ERBB2 was detected in 22% and was associated with stage (P=0.025). Cytoplasmic ERBB3 was associated with high tumour grade (P=0.01) and with ERBB2 positivity. In cell lines, NRG1β expression was significantly inversely related to ERBB3, but this was not confirmed in tumours.
There is a wide spectrum of NRG1 and ERBB receptor expression in bladder cancer. In advanced tumours, EGFR, ERBB2 and ERBB3 upregulation is common and there is a relationship between expression of ERBB2 and ERBB3 but not the NRG1 ligand.
针对 ERBB2 的治疗在临床上已取得成效。然而，反应不仅仅取决于 ERBB2 的表达。其首选异二聚化伙伴 ERBB3 的水平和 ERBB 配体也可能发挥作用。
我们通过实时定量 RT-PCR 测量了膀胱肿瘤和细胞系中 NRG1 的表达，通过 Western blot 和免疫组化测量了 ERBB 受体。
NRG1α 和 NRG1β 表现出显著的协调表达。NRG1β 在 78%的细胞系中上调。在肿瘤中，表达范围更大，随着分期和分级的升高，NRG1α 呈上升趋势。在 15%的细胞系（EGFR）、20%（ERBB2）、41%（ERBB3）和 0%（ERBB4）中检测到 ERBB 蛋白表达增加。在 28%的肿瘤中检测到高 EGFR 表达，与分级和分期相关（P=0.05；P=0.04）。在 22%的肿瘤中检测到中等或高表达的 ERBB2，与分期相关（P=0.025）。细胞质 ERBB3 与高肿瘤分级相关（P=0.01），并与 ERBB2 阳性相关。在细胞系中，NRG1β 的表达与 ERBB3 呈显著负相关，但在肿瘤中未得到证实。
在膀胱癌中存在广泛的 NRG1 和 ERBB 受体表达谱。在晚期肿瘤中，EGFR、ERBB2 和 ERBB3 的上调很常见，并且 ERBB2 和 ERBB3 的表达之间存在关系，但与 NRG1 配体无关。
