title: Deep Infiltrating Endometriosis and Endometrial Adenocarcinoma Express High Levels of Myostatin and Its Receptors Messenger RNAs.
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.
authors.affiliation: 1 Department of Molecular and Developmental Medicine, Obstetrics and Gynecology, University of Siena, Siena, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Carrarelli
authors.affiliation: 1 Department of Molecular and Developmental Medicine, Obstetrics and Gynecology, University of Siena, Siena, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Funghi
authors.affiliation: 2 Department of Experimental and Clinical Medicine, Università Politecnica delle Marche, Ancona, Italy.|3 Department of Information Engineering, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Pasquapina
authors.initials: P
authors.lastname: Ciarmela
authors.affiliation: 1 Department of Molecular and Developmental Medicine, Obstetrics and Gynecology, University of Siena, Siena, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Centini
authors.affiliation: 4 Division of Human Reproduction, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Fernando M
authors.initials: FM
authors.lastname: Reis
authors.affiliation: 4 Division of Human Reproduction, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Dela Cruz
authors.affiliation: 5 Division of Obstetrics and Gynecology, Careggi University Hospital, Florence, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Mattei
authors.affiliation: 1 Department of Molecular and Developmental Medicine, Obstetrics and Gynecology, University of Siena, Siena, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Vannuccini
authors.affiliation: 1 Department of Molecular and Developmental Medicine, Obstetrics and Gynecology, University of Siena, Siena, Italy.
authors.forename: Felice
authors.initials: F
authors.lastname: Petraglia
mesh_terms: D030201:Activin Receptors, Type I / Q000378:metabolism; D030301:Activin Receptors, Type II / Q000378:metabolism; D000328:Adult; D000368:Aged; D018269:Carcinoma, Endometrioid / Q000378:metabolism*; D016889:Endometrial Neoplasms / Q000378:metabolism*; D004715:Endometriosis / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D008597:Menstrual Cycle; D008875:Middle Aged; D055435:Myostatin / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D055815:Young Adult
chemical_list: C525911:MSTN protein, human; D055435:Myostatin; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; C498932:ACVR1B protein, human; D030201:Activin Receptors, Type I; D030301:Activin Receptors, Type II; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625841:TGFBR1 protein, human; C425584:activin receptor type II-B
keywords: endometrial adenocarcinoma; endometrial polyps; endometriosis; endometrium; myostatin