Department of Cell Biology and Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Int J Mol Sci. 2023 Jan 31;24(3):2690. doi: 10.3390/ijms24032690.
Adenomyosis is defined as the development of endometrial epithelial glands and stroma within the myometrial layer of the uterus. These "ectopic" lesions share many cellular characteristics with endometriotic epithelial cells as well as endometrial adenocarcinoma cells, including enhanced proliferation, migration, invasion and progesterone resistance. We recently reported that the 60S acidic ribosomal protein P1, RPLP1, is up-regulated in endometriotic epithelial cells and lesion tissue where it plays a role in cell survival. To evaluate if a similar pattern of expression and function for RPLP1 exists in adenomyosis and endometrial cancer, we examined RPLP1 expression in adenomyosis and endometrial cancer tissue specimens and assessed its function in vitro using well-characterized cell lines. A total of 12 control endometrial biopsies and 20 eutopic endometrial and matched adenomyosis biopsies as well as 103 endometrial adenocarcinoma biopsies were evaluated for RPLP1 localization by immunohistochemistry. Endometrial adenocarcinoma cell lines, Ishikawa, HEC1A, HEC1B and AN3 were evaluated for RPLP1 protein and transcript expression, while in vitro function was evaluated by knocking down RPLP1 expression and assessing cell survival and migration. RPLP1 protein was up-regulated in eutopic epithelia as well as in adenomyosis lesions compared to eutopic endometria from control subjects. RPLP1 was also significantly up-regulated in endometrial adenocarcinoma tissue. Knockdown of RPLP1 in endometrial adenocarcinoma cell lines was associated with reduced cell survival and migration. RPLP1 expression is up-regulated in eutopic and ectopic adenomyotic epithelia as well as in the epithelia of endometrial cancer specimens. In vitro studies support an essential role for RPLP1 in mediating cell survival and migration, processes which are all involved in pathophysiology associated with both diseases.
腺肌病是指子宫内膜上皮腺体和间质在子宫肌层内的发育。这些“异位”病变与子宫内膜异位症上皮细胞和子宫内膜腺癌细胞具有许多细胞特征，包括增强的增殖、迁移、侵袭和孕激素抵抗。我们最近报道，60S 酸性核糖体蛋白 P1（RPLP1）在子宫内膜异位症上皮细胞和病变组织中上调，在那里它在细胞存活中起作用。为了评估 RPLP1 在腺肌病和子宫内膜癌中的表达和功能是否存在类似模式，我们检查了腺肌病和子宫内膜癌组织标本中的 RPLP1 表达，并使用经过充分表征的细胞系评估了其在体外的功能。总共评估了 12 个对照子宫内膜活检和 20 个在位子宫内膜和匹配的腺肌病活检以及 103 个子宫内膜腺癌活检，通过免疫组织化学评估 RPLP1 的定位。评估了子宫内膜腺癌细胞系 Ishikawa、HEC1A、HEC1B 和 AN3 的 RPLP1 蛋白和转录表达，而体外功能通过敲低 RPLP1 表达并评估细胞存活和迁移来评估。与对照受试者的在位子宫内膜相比，RPLP1 在在位上皮和腺肌病病变中均上调。RPLP1 在子宫内膜腺癌组织中也显著上调。在子宫内膜腺癌细胞系中敲低 RPLP1 与细胞存活和迁移减少有关。RPLP1 在在位和异位腺肌病上皮以及子宫内膜癌标本的上皮中表达上调。体外研究支持 RPLP1 在介导细胞存活和迁移中的重要作用，这些过程均与这两种疾病的病理生理学有关。
