title: Suppression of GNAI2 message in ovarian cancer.
abstract: BACKGROUND
  Understanding the integration of hormone signaling and how it impacts oncogenesis is critical for improved cancer treatments. Here we elucidate GNAI2 message alterations in ovarian cancer (OvCa). GNAI2 is a heterotrimeric G protein which couples cell surface hormone receptors to intracellular enzymes, and is best characterized for its direct role in regulating cAMP response element-binding protein (CREB) function by decreasing intracellular cAMP through inhibiting adenylyl cyclase.
  
  
  METHODS
  We probed the Origene human OvCa array for the presence of polymorphisms and gene expression alterations of GNAI2 using directing sequencing and qPCR. These data were supported by database mining of the [NCBI NIH GSE:6008, GSE:14764, GSE:29450, GDS:4066, GDS:3297, GSE:32474, and GSE:2003] datasets.
  
  
  RESULTS
  No significant polymorphisms were found, including an absence of the gip2 oncogene. However, 85.9% of (506 of 589) OvCa patients had decreased GNAI2 message. Further characterization demonstrated that the GNAI2 message was on average decreased 54% and maximally decreased by 2.8 fold in clear cell carcinoma. GNAI2 message decreased in early stage cancer while message was increased compared to normal in advanced cancers. The changes in GNAI2 also correlated to deregulation of CREB, Fos, Myc, cyclins, Arf, the transition from estrogen dependence to independence, and metastatic potential.
  
  
  CONCLUSIONS
  These data strongly implicate GNAI2 as a critical regulator of oncogenesis and an upstream driver of cancer progression in OvCa.
authors.forename: John R
authors.initials: JR
authors.lastname: Raymond
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Appleton
authors.forename: Jennifer Y
authors.initials: JY
authors.lastname: Pierce
authors.affiliation: Department of Drug Discovery and Biomedical Sciences, College of Pharmacy Medical University of South Carolina, 280 Calhoun St, QF415, Charleston, SC 29425, USA. petersy@musc.edu.
authors.forename: Yuri K
authors.initials: YK
authors.lastname: Peterson
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D002277:Carcinoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D057225:Data Mining; D030541:Databases, Genetic; D015536:Down-Regulation; D005260:Female; D051960:GTP-Binding Protein alpha Subunit, Gi2 / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D059467:Transcriptome
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; C498015:GNAI2 protein, human; D051960:GTP-Binding Protein alpha Subunit, Gi2