title: Differential activation of IGF-II promoters P3 and P4 in Caco-2 cells during growth and differentiation.
abstract: OBJECTIVE
  Insulin-like growth factor (IGF)-II gene is overexpressed in colon cancers. Transcriptional up-regulation may be the major mechanism contributing to its overexpression. IGF-II messenger RNA (mRNA) levels are up-regulated during proliferation followed by a significant decline during differentiation of Caco-2 cells. Mechanisms underlying transcriptional regulation of the IGF-II gene promoters (P1-P4) have yet to be examined in colon cancers, which was the basis for this study.
  
  
  METHODS
  Ribonuclease protection assay was used to measure IGF-II mRNA derived from P1-P4. To determine if changes in the IGF-II transcripts reflected differences in promoter activity, transient transfection assays with the full-length P1-P4-luciferase expression vectors were performed.
  
  
  RESULTS
  Both P3- and P4-derived transcripts were significantly up-regulated during the proliferative phase of the cells (days 3-6 in culture) and declined rapidly in cells undergoing differentiation (days 7-10); conversely, P1- and P2-derived transcripts were not detected. Similarly, transcriptional activity of P3 and P4 promoters reached peak levels by days 4-6 and declined rapidly thereafter. P1 and P2 were relatively inactive on all days.
  
  
  CONCLUSIONS
  The activity of the P3 and P4 promoters may play a selective role in regulating IGF-II mRNA levels during growth and differentiation of colon cancer cells.
authors.affiliation: Department of Anatomy and Neurosciences, University of Texas Medical Branch, Galveston, USA. posingh@mbian.UTMB.edu
authors.forename: P
authors.initials: P
authors.lastname: Singh
authors.forename: B
authors.initials: B
authors.lastname: Dai
authors.forename: R L
authors.initials: RL
authors.lastname: Given
authors.forename: X
authors.initials: X
authors.lastname: Lu
authors.forename: P E
authors.initials: PE
authors.lastname: Holthuizen
mesh_terms: D018938:Caco-2 Cells / Q000473:pathology* / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors
chemical_list: D012333:RNA, Messenger; D007335:Insulin-Like Growth Factor II