Objectives Aaquaporins contribute to pathogenesis of Endometrial cancer. Our study presents the first screen of grade I and grade III endometrial cancer cell lines for all 13 AQP classes in response to physiological doses of estrogen and progesterone.

Methods Ishikawa (IKC, grade I) and MFE-280 (grade III) were assessed with estrogen and progesterone at relevant doses, at multiple time points for cell proliferation, motility (3D migration and invasion assays), and cytoskeletal organisation. Patterns of AQP expression were compared in IKC and MFE-280 by quantitative (q) PCR and western blot (WB).

Results Cell numbers, 3D migration and invasiveness were increased in IKC by estrogen and decreased by progesterone in a dose- and time-dependent manner. Estrogen induced formation of lamellipodia in IKC. The EC50 and IC50 values for estrogen and progesterone were 1nM and 100nM respectively. Transcript levels of AQPs 0, -2, -3, -4, -5, -8 were significantly decreased by estrogen and progesterone in IKC, whereas AQP11 and AQP12 were increased. In contrast, in MFE-280 cells, estrogen and progesterone caused an increase in transcript levels for AQPs 3,-4,-7, -8, whereas expression of AQPs 0, and -11 were decreased. Protein expression of AQP-1 and -4 was confirmed by WB.

Conclusions These findings indicate the potential role of aquaporins in progression and invasion of endometrial cancer, and highlight the previously unstudied AQPs 11 and 12 as targets of potential interest. Outcomes here provide a foundation for further exploration of aquaporin inhibitors in decreasing the progression of EC, and insights into new therapeutic strategies