title: The pattern of expression of Notch protein members in normal and pathological endometrium.
abstract: The objective of this study was to investigate the pattern of expression and the localization of Notch-1, Notch-4 and Jagged-1 in physiological and pathological human endometrium and to evaluate the expression levels of two major regulators of the G1 checkpoint, namely cyclin D1 and p21. Sixty samples of physiological endometrium and 60 samples of pathological endometrium were used for the study. Evaluation of the expression level and the distribution of Notch pathway members and cell-cycle proteins was performed by immunohistochemistry. In the physiological endometrium we observed an increase of Notch-1 and Jagged-1 from proliferative to secretory phase and an opposite trend for Notch-4. In menopause, the level of expression of all three members of the Notch pathway decreased. We also observed a cyclin D1 increase from proliferative to secretory phase. By contrast, p21 showed a slight increase from proliferative to secretory phase. In the pathological endometrium, we observed an increase of Notch-1 expression from polyps to carcinoma and decrease for Notch-4 and Jagged-1. Moreover, we observed a higher expression of cyclin D1 in all the endometrial pathologies. By contrast, the expression level of p21 slightly increased from polyps to carcinoma. We concluded that in human endometrium Notch-4 seems to be more involved in controlling proliferation, whereas Notch-1 seems to be more involved in differentiation programming. Deregulation of these functions may induce the onset of several endometrial pathologies from polyps to cancer.
authors.affiliation: Department of Gynaecology, Obstetric and Reproductive Science, Second University of Studies of Naples, Naples, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Cobellis
authors.forename: Francesca
authors.initials: F
authors.lastname: Caprio
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Trabucco
authors.forename: Annunziata
authors.initials: A
authors.lastname: Mastrogiacomo
authors.forename: Gabriele
authors.initials: G
authors.lastname: Coppola
authors.forename: Lucrezia
authors.initials: L
authors.lastname: Manente
authors.forename: Nicola
authors.initials: N
authors.lastname: Colacurci
authors.forename: Maria
authors.initials: M
authors.lastname: De Falco
authors.forename: Antonio
authors.initials: A
authors.lastname: De Luca
mesh_terms: D000704:Analysis of Variance; D015415:Biomarkers / Q000032:analysis; D002135:Calcium-Binding Proteins / Q000032:analysis; D002277:Carcinoma / Q000737:chemistry / Q000378:metabolism*; D019938:Cyclin D1 / Q000032:analysis; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000032:analysis; D004714:Endometrial Hyperplasia / Q000378:metabolism*; D016889:Endometrial Neoplasms / Q000737:chemistry / Q000378:metabolism*; D004717:Endometrium / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis; D000072100:Jagged-1 Protein; D008565:Membrane Proteins / Q000032:analysis; D008593:Menopause / Q000502:physiology; D008597:Menstrual Cycle / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000378:metabolism; D051881:Receptor, Notch1 / Q000032:analysis / Q000378:metabolism; D000074562:Receptor, Notch4; D051880:Receptors, Notch / Q000032:analysis / Q000378:metabolism*; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction / Q000502:physiology
chemical_list: D015415:Biomarkers; D002135:Calcium-Binding Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; C497761:NOTCH1 protein, human; C106075:NOTCH4 protein, human; D011518:Proto-Oncogene Proteins; D051881:Receptor, Notch1; D000074562:Receptor, Notch4; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins; D019938:Cyclin D1