Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
Cancer Res. 2011 Mar 1;71(5):1515-9. doi: 10.1158/0008-5472.CAN-10-3795. Epub 2011 Feb 22.
A subtype of HER2-positive tumors with distinct biological and clinical features expresses a series of carboxy-terminal fragments collectively known as p95HER2. One of these fragments, named 100- to 115-kDa p95HER2 or 611-CTF, is hyperactive because of its ability to form homodimers maintained by intermolecular disulfide bonds. Despite lacking the majority of the extracellular domain, this HER2 fragment drives breast cancer progression in vivo. The recent availability of specific anti-p95 antibodies has confirmed previous results indicating that the expression of p95HER2 is predictive of poor prognosis and correlates with resistance to the treatment with trastuzumab, a therapeutic antibody directed against the extracellular domain of HER2.
一种具有独特生物学和临床特征的 HER2 阳性肿瘤亚类表达一系列羧基末端片段，统称为 p95HER2。这些片段之一，命名为 100 至 115 kDa p95HER2 或 611-CTF，由于其能够形成由分子间二硫键维持的同源二聚体而具有高活性。尽管缺乏大部分细胞外结构域，但这种 HER2 片段在体内驱动乳腺癌的进展。最近出现的特异性抗 p95 抗体证实了先前的结果，表明 p95HER2 的表达是预后不良的预测因子，并与对曲妥珠单抗（一种针对 HER2 细胞外结构域的治疗性抗体）治疗的耐药性相关。
