Genetics and proteomics of pituitary tumors.
Genetics and proteomics determine structure and function of normal tissues, and the molecular alterations that underlie tumorigenesis result in changes in these aspects of tissue biology in neoplasms. We review the known genetic alterations in pituitary tumors. These include the oncogenic Gsalpha protein (GSP)-activating mutations, and pituitary tumor-derived fibroblast growth factor receptor-4 (ptd-FGFR4), as well as tumor suppressor gene mutations associated with multiple endocrine neoplasia type 1 (MEN1). Other candidates identified from expression profiling include pituitary tumor-transforming gene (PTTG), GADD45, and bone morphogenic protein (BMP)4. Proteomic changes in pituitary tumors include classical alterations identified by immunohistochemistry as well as epigenetic reductions in p27. The underlying mechanisms for dysregulated cell adhesive molecules including cadherins and FGFRs are reviewed. The combined use of genetic and proteomic approaches will enhance novel drug therapeutic development.
Asa
Sylvia L
SL
Endocrine Oncology Site Group, Mount Sinai and Princess Margaret Hospitals, University of Toronto, Toronto, Ontario, Canada. sylvia.asa@uhn.on.ca
Ezzat
Shereen
S
D000236:Adenoma / Q000235:genetics* / Q000378:metabolism*; D044385:GTP-Binding Protein alpha Subunits / Q000096:biosynthesis / Q000235:genetics; D020869:Gene Expression Profiling; D016147:Genes, Tumor Suppressor; D013007:Growth Hormone-Releasing Hormone / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000378:metabolism*; D040901:Proteomics; D051499:Receptor, Fibroblast Growth Factor, Type 4 / Q000096:biosynthesis / Q000235:genetics
D044385:GTP-Binding Protein alpha Subunits; D013007:Growth Hormone-Releasing Hormone; C496371:FGFR4 protein, human; D051499:Receptor, Fibroblast Growth Factor, Type 4