Genetics, gene expression and bioinformatics of the pituitary gland.
Genetic cases of congenital pituitary hormone deficiency are common and many are caused by transcription factor defects. Mouse models with orthologous mutations are invaluable for uncovering the molecular mechanisms that lead to problems in organ development and typical patient characteristics. We are using mutant mice defective in the transcription factors PROP1 and POU1F1 for gene expression profiling to identify target genes for these critical transcription factors and candidates for cases of pituitary hormone deficiency of unknown aetiology. These studies reveal critical roles for Wnt signalling pathways, including the TCF/LEF transcription factors and interacting proteins of the groucho family, bone morphogenetic protein antagonists and targets of notch signalling. Current studies are investigating the roles of novel homeobox genes and pathways that regulate the transition from proliferation to differentiation, cell adhesion and cell migration. Pituitary adenomas are a common human health problem, yet most cases are sporadic, necessitating alternative approaches to traditional Mendelian genetic studies. Mouse models of adenoma formation offer the opportunity for gene expression profiling during progressive stages of hyperplasia, adenoma and tumorigenesis. This approach holds promise for the identification of relevant pathways and candidate genes as risk factors for adenoma formation, understanding mechanisms of progression, and identifying drug targets and clinically relevant biomarkers.
Davis
Shannon W
SW
University of Michigan, Ann Arbor, MI 48109-0618, USA.
Potok
Mary Anne
MA
Brinkmeier
Michelle L
ML
Carninci
Piero
P
Lyons
Robert H
RH
MacDonald
James W
JW
Fleming
Michelle T
MT
Mortensen
Amanda H
AH
Egashira
Noboru
N
Ghosh
Debashis
D
Steel
Karen P
KP
Osamura
Robert Y
RY
Hayashizaki
Yoshihide
Y
Camper
Sally A
SA
D000818:Animals; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics*; D019295:Computational Biology / Q000379:methods; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D051379:Mice; D008817:Mice, Mutant Strains; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics*; D010902:Pituitary Gland / Q000378:metabolism* / Q000473:pathology; D010907:Pituitary Hormones / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D010907:Pituitary Hormones