Overxpression of lysine specific demethylase 1 in ovarian endometriomas and its inhibition reduces cellular proliferation cell cycle progression and invasiveness

Lysine-specific demethylase 1 (LSD1) is overexpressed in endometriomas; treatment of endometriotic stromal cells with tranylcypromine, an LSD1 inhibitor, significantly reduces cellular proliferation, cell cycle progression, and invasiveness.

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Authors

Ding Ding, M.D., Ph.D., Xishi Liu, M.D., Ph.D., Sun-Wei Guo, Ph.D.

Volume 101, Issue 3, Pages 740-749, March 2014

Abstract

Objective:

To investigate whether lysine-specific demethylase 1 (LSD1) is aberrantly expressed in endometriomas and whether treatment with tranylcypromine, an LSD1 inhibitor, has any effect on cell viability, cell cycle, and invasiveness.

Design:

Laboratory study using human tissues.

Setting:

Academic hospital.

Patient(s):

Forty-two ectopic endometrial tissue samples, their homologue eutopic endometrial tissue samples, and 70 control endometrial tissue samples.

Intervention(s):

Immunohistochemistry analysis of LSD1 of all human tissue samples, and Western blot analysis, quantitative real-time reverse-transcription polymerase chain reaction analysis, cell viability assay, cell cycle analysis, and invasion assay of eutopic and ectopic endometriotic stromal cells and normal endometrial stromal cells.

Main Outcome Measure(s):

Immunostaining levels of LSD1, gene and protein expression levels, cell viability, cell cycles, and invasiveness.

Result(s):

The expression of the LSD1 gene and protein in endometriosis was elevated. Treatment of endometriotic stromal cells with tranylcypromine statistically significantly reduced the cellular proliferation, cell cycle progression, and invasiveness.

Conclusion(s):

Because DNA and histones are intimately intertwined and work in concert in transcription regulation, conceivably histone demethylation activity of LSD1 could be wide ranging. The inhibition of LSD1 activity by tranylcypromine and the resultant inhibition of proliferation, cell cycle progression, and invasiveness suggest that LSD1 may be a candidate therapeutic target for endometriosis.

Read the full text at: http://www.fertstert.org/article/S0015-0282(13)03293-7/fulltext


Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.

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