J Cancer 2019; 10(13):3028-3036. doi:10.7150/jca.30588

Research Paper

Estradiol and Progesterone Induced Differentiation and Increased Stemness Gene Expression of Human Fallopian Tube Epithelial Cells

Yu-Hsun Chang1,2, Dah-Ching Ding1,3,4, Tang-Yuan Chu3,4✉

1. Stem Cell Laboratory, Department of Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation; Hualien, Taiwan
2. Department of Pediatrics, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation; Tzu Chi University, Hualien, Taiwan
3. Department of Obstetrics and Gynecology, Hualien Tzu-Chi Hospital, Buddhist Tzu Chi Medical Foundation; Tzu Chi University, Hualien, Taiwan
4. Institute of Medical Sciences, Tzu Chi University; Hualien, Taiwan

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Citation:
Chang YH, Ding DC, Chu TY. Estradiol and Progesterone Induced Differentiation and Increased Stemness Gene Expression of Human Fallopian Tube Epithelial Cells. J Cancer 2019; 10(13):3028-3036. doi:10.7150/jca.30588. Available from http://www.jcancer.org/v10p3028.htm

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Abstract

Fallopian tube epithelial cells (FTECs) are thought to be the origin of epithelial ovarian cancer. However, the effect of the hormones on FTECs is unknown, and therefore, this study explored this effect. We successfully derived FTECs from the fallopian tube epithelial layer and treated them with estradiol and progesterone. Reverse transcription polymerase chain reaction was used to evaluate the gene expression of the FTECs' hormone receptors. Confocal and electron microscopy were used to evaluate the morphology of the FTECs after they were treated with hormones. Finally, quantitative PCR was used to evaluate the gene expression of the hormone-treated FTECs. The results showed that the FTECs exhibited cuboidal cell morphology and could be maintained at a constant proliferation rate. Furthermore, flow cytometry revealed that the FTECs expressed stem cell markers, such as SSEA3, SSEA4, and Lgr5. Moreover, the FTECs could express both estrogen and progesterone receptors. In a culture treated with 400 nM estrogen, the FTECs differentiated toward ciliated cells, whereas in a culture treated with estradiol or progesterone, the FTECs increased their expression of certain stem cell markers (SSEA3, SSEA4, and Aldh1) and stemness genes [Wnt (AXIN2, LGR5, LGR6, and OLFM4) and Notch (Hes1) signaling]. In conclusion, hormones may alter the gene expressions of FTECs, and these cells may provide new insights into how FTECs regenerate in response to hormones.

Keywords: Fallopian tube, epithelium, stem cells, differentiation, hormone