title: Emerging role of PLAG1 as a regulator of growth and reproduction.
abstract: Pleomorphic adenoma gene 1 (PLAG1) belongs to the PLAG family of zinc finger transcription factors along with PLAG-like 1 and PLAG-like 2. The PLAG1 gene is best known as an oncogene associated with certain types of cancer, most notably pleomorphic adenomas of the salivary gland. While the mechanisms of PLAG1-induced tumorigenesis are reasonably well understood, the role of PLAG1 in normal physiology is less clear. It is known that PLAG1 is involved in cell proliferation by directly regulating a wide array of target genes, including a number of growth factors such as insulin-like growth factor 2. This is likely to be a central mode of action for PLAG1 both in embryonic development and in cancer. The phenotype of Plag1 knockout mice suggests an important role for PLAG1 also in postnatal growth and reproduction, as PLAG1 deficiency causes growth retardation and reduced fertility. A role for PLAG1 in growth and reproduction is further corroborated by genome-wide association studies in humans and domestic animals in which polymorphisms in the PLAG1 genomic region are associated with body growth and reproductive traits. Here we review the current evidence for PLAG1 as a regulator of growth and fertility and discuss possible endocrine mechanisms involved.
authors.affiliation: Department of PhysiologyAnatomy and Microbiology, School of Life Sciences, La Trobe University, Bundoora, Victoria 3086, AustraliaDepartment of Clinical SciencesIntervention and Technology, Karolinska Institutet and Karolinska University Hospital, Huddinge, 141 86 Stockholm, SwedenDepartment of Human GeneticsKU Leuven, B-3000 Leuven, Belgium.
authors.forename: Almas R
authors.initials: AR
authors.lastname: Juma
authors.affiliation: Department of PhysiologyAnatomy and Microbiology, School of Life Sciences, La Trobe University, Bundoora, Victoria 3086, AustraliaDepartment of Clinical SciencesIntervention and Technology, Karolinska Institutet and Karolinska University Hospital, Huddinge, 141 86 Stockholm, SwedenDepartment of Human GeneticsKU Leuven, B-3000 Leuven, Belgium.
authors.forename: Pauliina E
authors.initials: PE
authors.lastname: Damdimopoulou
authors.affiliation: Department of PhysiologyAnatomy and Microbiology, School of Life Sciences, La Trobe University, Bundoora, Victoria 3086, AustraliaDepartment of Clinical SciencesIntervention and Technology, Karolinska Institutet and Karolinska University Hospital, Huddinge, 141 86 Stockholm, SwedenDepartment of Human GeneticsKU Leuven, B-3000 Leuven, Belgium.
authors.forename: Sylvia V H
authors.initials: SV
authors.lastname: Grommen
authors.affiliation: Department of PhysiologyAnatomy and Microbiology, School of Life Sciences, La Trobe University, Bundoora, Victoria 3086, AustraliaDepartment of Clinical SciencesIntervention and Technology, Karolinska Institutet and Karolinska University Hospital, Huddinge, 141 86 Stockholm, SwedenDepartment of Human GeneticsKU Leuven, B-3000 Leuven, Belgium.
authors.forename: Wim J M
authors.initials: WJ
authors.lastname: Van de Ven
authors.affiliation: Department of PhysiologyAnatomy and Microbiology, School of Life Sciences, La Trobe University, Bundoora, Victoria 3086, AustraliaDepartment of Clinical SciencesIntervention and Technology, Karolinska Institutet and Karolinska University Hospital, Huddinge, 141 86 Stockholm, SwedenDepartment of Human GeneticsKU Leuven, B-3000 Leuven, Belgium b.degroef@latrobe.edu.au.
authors.forename: Bert
authors.initials: B
authors.lastname: De Groef
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation; D006128:Growth; D006130:Growth Disorders / Q000209:etiology; D006801:Humans; D007246:Infertility / Q000209:etiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D012098:Reproduction; D017385:Sequence Homology
chemical_list: D004268:DNA-Binding Proteins; C104382:PLAG1 protein, human; C491264:Plag1 protein, mouse
keywords: growth; hypothalamo-pituitary-gonadal axis; insulin-like growth factors; pleomorphic adenoma gene 1; puberty; reproduction; zinc finger transcription factor