Willibald Marina, Wurster Isabel, Meisner Christoph, Vogel Ulrich, Seeger Harald, Mueck Alfred O, Fehm Tanja, Neubauer Hans
University of Düsseldorf, Department of Obstetrics and Gynecology, Düsseldorf, Germany.
Center of Neurology Department of Neurodegenerative Diseases Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
Horm Metab Res. 2017 Aug;49(8):595-603. doi: 10.1055/s-0043-113635. Epub 2017 Jul 12.
PGRMC1 is known to be highly expressed in breast cancer tissue and is associated with chemoresistance in breast cancer cells. However, its role in breast cancer signaling is not fully understood yet. In the present study, the expression status of PGRMC1 and its phosphorylated version (pPGRMC1) in breast cancer tissue and surrounding stroma before and after neoadjuvant therapy was examined to find a possible association to therapy response. Tissue biopsies of 69 breast cancer patients were analyzed by immunohistochemistry for expression levels of PGRMC1 and pPGRMC1. Expression status of PGRMC1 and pPGRMC1 in tumor tissue was compared with expression status of progesterone receptor (PR), estrogen receptor α (ERα), total estrogen receptor β (ERβ), ERβ1, ERβ2, the proliferation marker Ki-67, and human epidermal growth factor receptor 2 (HER2/neu). Correlations were calculated for expression of PGRMC1 and pPGRMC1 before and after neoadjuvant-therapy. PGRMC1 and pPGRMC1 were highly abundant in every breast cancer tissue sample. Considerably lower signals were detected in surrounding tissue. Further, PGRMC1 and pPGRMC1 abundance was found to correlate with ERβ expression. A lower level of pPGRMC1 could be found in post-therapy surgical specimens compared to specimens before treatment. Interestingly, patients with high PGRMC1 tumor levels showed worse response to anthracycline-based therapy as patients with lower PGRMC1 levels. These new findings demonstrate that PGRMC1 might play an important role in progression and therapy resistance of human breast tumors and could offer an interesting target for anticancer therapy.
已知PGRMC1在乳腺癌组织中高表达，且与乳腺癌细胞的化疗耐药性有关。然而，其在乳腺癌信号传导中的作用尚未完全明确。在本研究中，检测了新辅助治疗前后乳腺癌组织及周围基质中PGRMC1及其磷酸化形式（pPGRMC1）的表达状态，以寻找与治疗反应的可能关联。通过免疫组织化学分析69例乳腺癌患者的组织活检标本中PGRMC1和pPGRMC1的表达水平。将肿瘤组织中PGRMC1和pPGRMC1的表达状态与孕激素受体（PR）、雌激素受体α（ERα）、总雌激素受体β（ERβ）、ERβ1、ERβ2、增殖标志物Ki-67和人表皮生长因子受体2（HER2/neu）的表达状态进行比较。计算新辅助治疗前后PGRMC1和pPGRMC1表达的相关性。PGRMC1和pPGRMC1在每个乳腺癌组织样本中含量都很高。在周围组织中检测到的信号明显较低。此外，发现PGRMC1和pPGRMC1的丰度与ERβ表达相关。与治疗前的标本相比，治疗后的手术标本中pPGRMC1水平较低。有趣的是，与PGRMC1水平较低的患者相比，PGRMC1肿瘤水平高的患者对蒽环类药物治疗的反应较差。这些新发现表明，PGRMC1可能在人类乳腺肿瘤的进展和治疗耐药中起重要作用，并可能为抗癌治疗提供一个有趣的靶点。
