title: Involvement of the transcription factor FoxM1 in contact inhibition.
abstract: Contact inhibition is a crucial mechanism regulating proliferation in vitro and in vivo. Although it is generally accepted that contact inhibition plays a pivotal role in maintaining tissue homeostasis, the molecular mechanisms of contact inhibition are still not fully understood. FoxM1 is known as a proliferation-associated transcription factor and is upregulated in many cancer types. Vice versa, anti-proliferative signals, such as TGF-β and differentiation signals decrease FoxM1 expression. Here we investigated the role of FoxM1 in contact inhibition in fibroblasts. We show that protein expression of FoxM1 is severely and rapidly downregulated upon contact inhibition, probably by inhibition of ERK activity, which then leads to decreased expression of cyclin A and polo-like kinase 1. Vice versa, ectopic expression of FoxM1 prevents the decrease in cyclin A and polo-like kinase 1 and causes a two-fold increase in saturation density indicating loss of contact inhibition. Hence, we show that downregulation of FoxM1 is required for contact inhibition by regulating expression of cyclin A and polo-like kinase 1.
authors.affiliation: Institute of Toxicology, Medical Center of the Johannes Gutenberg-University, Obere Zahlbacherstr. 67, 55131 Mainz, Germany.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Faust
authors.forename: Firas
authors.initials: F
authors.lastname: Al-Butmeh
authors.forename: Berenike
authors.initials: B
authors.lastname: Linz
authors.forename: Cornelia
authors.initials: C
authors.lastname: Dietrich
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics; D003260:Contact Inhibition; D019925:Cyclin A / Q000096:biosynthesis / Q000235:genetics; D015536:Down-Regulation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D059585:G1 Phase Cell Cycle Checkpoints; D051379:Mice; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D000097869:Polo-Like Kinase 1
chemical_list: D018797:Cell Cycle Proteins; D019925:Cyclin A; D048049:Extracellular Signal-Regulated MAP Kinases; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D000097869:Polo-Like Kinase 1; C491524:Foxm1 protein, mouse