Deep Infiltrating Endometriosis and Endometrial Adenocarcinoma Express High Levels of Myostatin and Its Receptors Messenger RNAs

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This study found high messenger RNA expression of myostatin and its receptors in deep infiltrating endometriosis and endometrial adenocarcinoma compared to control endometrium.

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This study measured myostatin mRNA and mRNA for its receptors ALK4, ALK5, and ActRIIB in endometrial tissue from healthy women across the menstrual cycle, and compared expression in tissues from benign conditions (deep infiltrating endometriosis, ovarian endometrioma, and endometrial polyps) and in malignant endometrial adenocarcinoma, using quantitative real-time PCR on RNA from hysteroscopic, laparoscopic, and hysterectomy samples. Myostatin and its receptor mRNAs were expressed throughout the menstrual cycle in healthy endometrium without differences between proliferative and secretory phases. The highest myostatin mRNA expression occurred in deep infiltrating endometriosis and endometrial carcinoma, and myostatin receptor mRNA was also higher in deep infiltrating endometriosis and adenocarcinomas versus control; receptor-specific increases were reported in ovarian endometrioma and polyps. The study’s caveat is that it assessed mRNA expression levels from tissue homogenates, without functional testing of myostatin signaling in this cohort. This paper is centrally about endometriosis — it reports increased myostatin and receptor mRNA expression in deep infiltrating endometriosis alongside endometrial adenocarcinoma.

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Abstract

Myostatin is a growth factor member of the transforming growth factor β superfamily, which is known to play major roles in cell proliferation and differentiation. The present study investigated the messenger RNA (mRNA) expression of myostatin and myostatin receptors (activin receptor-like kinase 4 [ALK4], transforming growth factor (TGF)-β type I receptor kinase [ALK5] and activin receptor type IIB [ActRIIB]) in endometrium of healthy women during menstrual cycle as well as in benign (endometriosis, polyps) and malignant (endometrial adenocarcinoma) conditions. Endometrial specimens were collected by hysteroscopy, whereas endometriotic lesions were collected by laparoscopy, and adenocarcinomas were sampled after hysterectomy. Total RNA was extracted from tissue homogenates, and gene expression was assessed by quantitative real-time polymerase chain reaction. Myostatin and myostatin receptors mRNAs were expressed by healthy endometrium throughout the menstrual cycle, with no differences between the proliferative and secretory phase. The highest myostatin mRNA expression was found in patients with deep infiltrating endometriosis (DIE) and in endometrial carcinoma; expression was also found in ovarian endometrioma (OMA ) and endometrial polyps. Myostatin receptors mRNA expression was higher in DIE and adenocarcinomas compared to control endometrium. The expression of ALK5 and ActRIIB in OMA was higher than in controls, whereas polyps had an increased expression of ALK5 mRNA. In conclusion, the present data showed for the first time the expression of myostatin in healthy endometrium and a higher expression in endometriosis and endometrial cancer, suggesting myostatin involvement in human endometrial physiology and related pathologies.
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Abstract

Myostatin is a growth factor member of the transforming growth factor β superfamily, which is known to play major roles in cell proliferation and differentiation. The present study investigated the messenger RNA (mRNA) expression of myostatin and myostatin receptors (activin receptor-like kinase 4 [ALK4], transforming growth factor (TGF)-β type I receptor kinase [ALK5] and activin receptor type IIB [ActRIIB]) in endometrium of healthy women during menstrual cycle as well as in benign (endometriosis, polyps) and malignant (endometrial adenocarcinoma) conditions. Endometrial specimens were collected by hysteroscopy, whereas endometriotic lesions were collected by laparoscopy, and adenocarcinomas were sampled after hysterectomy. Total RNA was extracted from tissue homogenates, and gene expression was assessed by quantitative real-time polymerase chain reaction. Myostatin and myostatin receptors mRNAs were expressed by healthy endometrium throughout the menstrual cycle, with no differences between the proliferative and secretory phase. The highest myostatin mRNA expression was found in patients with deep infiltrating endometriosis (DIE) and in endometrial carcinoma; expression was also found in ovarian endometrioma (OMA ) and endometrial polyps. Myostatin receptors mRNA expression was higher in DIE and adenocarcinomas compared to control endometrium. The expression of ALK5 and ActRIIB in OMA was higher than in controls, whereas polyps had an increased expression of ALK5 mRNA. In conclusion, the present data showed for the first time the expression of myostatin in healthy endometrium and a higher expression in endometriosis and endometrial cancer, suggesting myostatin involvement in human endometrial physiology and related pathologies. Similar content being viewed by others

References

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Condition tags

endometriosisdie_deep_infiltrating

MeSH descriptors

Carcinoma, Endometrioid Endometrial Neoplasms Endometriosis Myostatin Protein Serine-Threonine Kinases Activin Receptors, Type I Activin Receptors, Type I Activin Receptors, Type II Activin Receptors, Type II Adult Aged Carcinoma, Endometrioid Endometrial Neoplasms Endometriosis Female Gene Expression Humans Menstrual Cycle Middle Aged Myostatin

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