Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China.
Department of Pathology, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China.
Sci Rep. 2019 Jan 31;9(1):1032. doi: 10.1038/s41598-018-37648-7.
PES1, a BRCT domain-containing protein, has been shown to play a role in modulating the balance and ratio between ERα and ERβ protein, which is involved in the occurrence and development of breast and ovarian cancer. However, its role in connection with the balance and ratio between ERα and ERβ protein in papillary thyroid cancer (PTC) remains unclear. Here, we found that ERα and ERβ were co-expressed in human PTC tissues and cells. ERα promoted and ERβ inhibited the proliferation, invasion and migration of PTC cells. PES1 modulated the balance between ERα and ERβ by elevating the ERα protein level and simultaneously reducing the ERβ protein level, then upregulating the ERα/ERβ protein ratio and promoting the proliferation, invasion and migration of PTC cells. In PTC tissues, PES1 protein level was positively correlated with the ERα protein level and negatively correlated with the ERβ protein level. The PES1 and ERα protein levels were gradually increased and the ERβ protein level was decreased by degree in the occurrence and development of PTC. Increased PES1 and ERα protein levels and decreased ERβ protein level were correlated with the aggressive behaviors of PTC patients such as large tumor size, extrathyroidal extension (ETE), lymph node metastasis (LNM), high BRAFV600E expression and high TNM stage. It is suggested that PES1 promotes the occurrence and development of PTC by elevating the ERα protein level and reducing the ERβ protein level, and then upregulating the ERα/ERβ protein ratio.
PES1 是一种含有 BRCT 结构域的蛋白质，已被证明在调节 ERα 和 ERβ 蛋白之间的平衡和比例方面发挥作用，而这种平衡和比例参与了乳腺癌和卵巢癌的发生和发展。然而，其在甲状腺乳头状癌（PTC）中与 ERα 和 ERβ 蛋白平衡和比例的关系尚不清楚。在这里，我们发现 ERα 和 ERβ 在人 PTC 组织和细胞中共同表达。ERα 促进，ERβ 抑制 PTC 细胞的增殖、侵袭和迁移。PES1 通过提高 ERα 蛋白水平，同时降低 ERβ 蛋白水平，从而调节 ERα 和 ERβ 之间的平衡，上调 ERα/ERβ 蛋白比值，促进 PTC 细胞的增殖、侵袭和迁移。在 PTC 组织中，PES1 蛋白水平与 ERα 蛋白水平呈正相关，与 ERβ 蛋白水平呈负相关。PES1 和 ERα 蛋白水平在 PTC 的发生和发展过程中逐渐升高，ERβ 蛋白水平逐渐降低。PES1 和 ERα 蛋白水平的增加和 ERβ 蛋白水平的降低与 PTC 患者的侵袭性行为相关，如肿瘤体积大、甲状腺外侵犯（ETE）、淋巴结转移（LNM）、高 BRAFV600E 表达和高 TNM 分期。提示 PES1 通过提高 ERα 蛋白水平和降低 ERβ 蛋白水平，上调 ERα/ERβ 蛋白比值，促进 PTC 的发生和发展。
