Altered expression of the tachykinins substance P/neurokinin A/hemokinin-1 and their preferred neurokinin 1/neurokinin 2 receptors in uterine leiomyomata

Tachykinin family members are widely expressed throughout the female genital tract and increasingly involved in cancer proliferation. This study demonstrates that the whole tachykinin system is differentially regulated in leiomyomas.

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Volume 106, Issue 6, Pages 1521-1529

Authors:

Ayoze González-Santana, M.Sc., Sara Marrero-Hernández, M.Sc., Idaira Dorta, Ph.D., Mariano Hernández, Ph.D., Francisco María Pinto, Ph.D., Delia Báez, M.D., Ph.D., Aixa R. Bello, Ph.D., Luz Candenas, Ph.D., Teresa A. Almeida, Ph.D.

Abstract:

Objective

To study the expression levels of tachykinins and tachykinin receptors in uterine leiomyomas and matched myometrium.

Design

Laboratory study.

Setting

University research laboratories and academic hospital.

Patient(s)

Women undergoing hysterectomy for symptomatic leiomyomas.

Intervention(s)

Quantitative polymerase chain reaction, immunohistochemistry and Western blot.

Main Outcome Measure(s)

Expression and tissue immunostaining of substance P, neurokinin A, hemokinin-1, neurokinin 1 receptor full-length (NK1R-Fl) and truncated (NK1R-Tr) isoforms, and neurokinin 2 receptor (NK2R) in paired samples of leiomyoma and adjacent normal myometrium.

Result(s)

TAC1 messenger RNA (mRNA) was significantly up-regulated in leiomyomas, whereas intense immunoreaction for the three peptides was particularly abundant in connective tissue cells. Differential regulation of TACR1 mRNA was observed, and at the protein level there was a significant increased expression of NK1R short isoform (NK1R-Tr). TACR2 mRNA was significantly up-regulated in leiomyomas, although levels of NK2R protein were similar in normal and tumor cells.

Conclusion(s)

These and our previous data demonstrate that the whole tachykinin system is differentially regulated in leiomyomas. The increased expression of NK1R-Tr might stimulate leiomyoma growth in a similar way to that observed in other steroid-dependent tumors.


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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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