Department of Clinical Laboratory, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, P.R. China.
Institute of Bioinformatics, School of Agriculture and Biological Technology, Zhejiang University, Hangzhou, Zhejiang 310029, P.R. China.
Mol Med Rep. 2017 Aug;16(2):1445-1450. doi: 10.3892/mmr.2017.6713. Epub 2017 Jun 7.
Insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) is a potential tumor‑suppressor gene in various cancers. However, its biological role and underlying mechanism has not been well investigated in endometrial cancer yet. The aim of the present study aimed to investigate the role and underlying molecular mechanisms of IGFBP‑rP1 in endometrial cancer cells in vitro. The authors used transfection of IGFBP‑rP1 or small interfering (si)RNA in endometrial cancer HEC‑1A or Ishikawa cells, respectively. Biological functional alterations, such as cell growth and cell cycle were analyzed in endometrial cancer cells, combined with the use of PD98059. A panel of proteins including phospho‑retinoblastoma (p‑RB) and p‑extracellular signal‑regulated kinase (ERK)/ERK were detected by western blot analysis. It was observed that IGFBP‑rP1 transfection inhibited cell growth, and induced G1 phase arrest and cellular senescence in HEC‑1A cells while gene silencing presented the adverse functional changes. Moreover, p‑RB and p‑ERK were significantly downregulated or upregulated in HEC‑1A‑IGFBP‑rP1 cells or Ishikawa‑siRNA (IGFBP‑rP1) compared with control cells, respectively. These observations were reinforced in endometrial cancer cells by PD98059 treatment. The authors conclude that IGFBP‑rP1 acts as a potential tumor suppressor via the suppression of the ERK signaling pathway in endometrial cancer cells. These findings suggested that IGFBP‑rP1 may serve as a potential therapeutic target for cancer intervention in the future.
胰岛素样生长因子结合蛋白相关蛋白 1（IGFBP-rP1）是多种癌症中的一种潜在的肿瘤抑制基因。然而，其在子宫内膜癌中的生物学作用和潜在机制尚未得到充分研究。本研究旨在探讨 IGFBP-rP1 在子宫内膜癌细胞中的作用及其潜在的分子机制。作者分别通过 IGFBP-rP1 转染或小干扰（si）RNA 在子宫内膜癌细胞 HEC-1A 或 Ishikawa 中进行实验。通过 PD98059 联合分析，检测了子宫内膜癌细胞的生物学功能改变，如细胞生长和细胞周期。采用 Western blot 分析检测了一组包括磷酸化视网膜母细胞瘤（p-RB）和 p-细胞外信号调节激酶（ERK）/ERK 的蛋白。结果观察到 IGFBP-rP1 转染抑制了 HEC-1A 细胞的生长，并诱导 G1 期阻滞和细胞衰老，而基因沉默则呈现出相反的功能变化。此外，与对照细胞相比，HEC-1A-IGFBP-rP1 细胞或 Ishikawa-siRNA（IGFBP-rP1）中的 p-RB 和 p-ERK 表达明显下调或上调。PD98059 处理进一步证实了这些在子宫内膜癌细胞中的观察结果。作者得出结论，IGFBP-rP1 通过抑制 ERK 信号通路在子宫内膜癌细胞中发挥潜在的肿瘤抑制作用。这些发现表明，IGFBP-rP1 可能成为未来癌症干预的潜在治疗靶点。
