title: Spatial-temporal protein expression of inhibitor of differentiation-1 (Id1) during fetal embryogenesis and in different mouse and human cancer types.
abstract: Inhibitor of differentiation-1 (Id1) plays a role in cell proliferation, acquisition of epithelial to mesenchymal transition (EMT) features and angiogenesis. Id1 was shown to be expressed in some tumor types, mainly in advanced dedifferentiated stages. However, recent studies using a validated and highly specific monoclonal antibody against Id1 have challenged many of the results obtained by immunohistochemistry. The goal of our work was to perform a thorough analysis of Id1 expression in mouse embryos and adult tissues, as well as healthy and malignant mouse and human samples using this validated antibody (Perk et al., 2006). Our results show that Id1 was highly expressed in the oropharyngeal cavity, lung, cartilage and skin of E14 and E15 mouse embryos, but expression was progressively reduced in more developed embryos. Immunostaining only remained in epithelial cells of the gut and uterus of adult mice. Mammary MMTV-Myc and MMTV-Myc/VEGF transgenic mouse tumors, and squamous cell carcinomas of the lung induced by N-nitroso-tris-chloroethylurea (NTCU) were highly positive for Id1, unlike their respective healthy counterparts. Id1 immunostaining in a human tissue microarray (TMA) revealed strong expression in cancers of the oral cavity, bladder and cervix. Some tumor specimens of esophagus, thyroid and breast were also strongly positive. Our results suggest that Id1 is an oncofetal protein highly expressed in particular tumor types that should be reanalyzed in future studies using large cohorts of patients to reassess its diagnostic/prognostic value. Moreover, MMTV-Myc- and NTCU-induced tumors could serve as appropriate mouse models to study Id1 functions in breast and lung cancer, respectively.
authors.affiliation: Oncology Division, Center for Applied Medical Research, CIMA, University of Navarra, Pamplona, Spain.
authors.forename: Miriam
authors.initials: M
authors.lastname: Redrado
authors.forename: Elena
authors.initials: E
authors.lastname: Bodegas
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Villaro
authors.forename: Paul A
authors.initials: PA
authors.lastname: Nguewa
authors.forename: Ines
authors.initials: I
authors.lastname: Lopez
authors.forename: Ignacio
authors.initials: I
authors.lastname: Gil-Bazo
authors.forename: Alfonso
authors.initials: A
authors.lastname: Calvo
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D002294:Carcinoma, Squamous Cell / Q000378:metabolism; D004622:Embryo, Mammalian; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007150:Immunohistochemistry; D051798:Inhibitor of Differentiation Protein 1 / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D046228:Microarray Analysis; D009368:Neoplasm Transplantation; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D000911:Antibodies, Monoclonal; C497453:ID1 protein, human; C497455:Idb1 protein, mouse; D051798:Inhibitor of Differentiation Protein 1