title: Effects of SRC and STAT3 upon gap junctional, intercellular communication in lung cancer lines.
abstract: BACKGROUND
  We have previously demonstrated a positive correlation between SRC and its effector signal transducer and activator of transcription-3 (STAT3), and a reverse relation between SRC and gap junctional communication (GJIC) in seven non-small cell lung cancer (NSCLC) lines. Since a number of oncogenes besides SRC can affect GJIC, here we examined the actual contribution of the SRC/STAT3 axis to GJIC suppression.
  
  
  METHODS
  SRC and STAT3 activity levels were examined in SK-LuCi-6, LC-T, QU-DB, SW-1573, BH-E, Calu-6, FR-E, SK-MES, H1299, BEN, WT-E, A549 and SHP-77 cells by western blott analysis, probing with antibodies specific for SRC-ptyr418 or STAT3-ptyr705. GJIC was examined by in situ electroporation.
  
  
  RESULTS
  Confluence of all cultured NSCLC cells tested induces a dramatic increase in STAT3 activity, which is independent of SRC action. In addition, the LC-T line had high STAT3-705, despite the fact that SRC-418 expression was low, indicating that other, SRC-independent factors must be responsible for STAT3 activation and GJIC suppression in these cells; however, BH-E and SHP-77 cells with low GJIC, both SRC-418 and STAT3-705 expression were low, indicating that GJIC suppression can be independent of the SRC/STAT3 axis altogether. Our results also show that STAT3 inhibition does not restore GJIC in any of the examined lines, while in the non-transformed rat F111 fibroblast line which has extensive GJIC, STAT3 inhibition actually eliminated junctional permeability.
  
  
  CONCLUSIONS
  Our results indicate a further level of complexity in the relationship between SRC, STAT3 and GJIC in NSCLC than what has been previously demonstrated. In addition, STAT3 is actually required for, rather than suppressing GJIC.
authors.affiliation: Department of Biomedical and Molecular Sciences, Botterell Hall, Room 713, Queen's University, Kingston, Ontario, Canada K7L 3N6. raptisl@queensu.ca.
authors.forename: Mulu
authors.initials: M
authors.lastname: Geletu
authors.forename: Stephanie
authors.initials: S
authors.lastname: Guy
authors.forename: Leda
authors.initials: L
authors.lastname: Raptis
mesh_terms: D000818:Animals; D002450:Cell Communication; D045744:Cell Line, Tumor; D000069439:Dasatinib; D015536:Down-Regulation; D017629:Gap Junctions / Q000502:physiology*; D015870:Gene Expression; D006801:Humans; D008175:Lung Neoplasms; D011728:Pyridones / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D013844:Thiazoles / Q000494:pharmacology; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D011728:Pyridones; D011743:Pyrimidines; C107953:RAC1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D013844:Thiazoles; D019061:src-Family Kinases; D020830:rac1 GTP-Binding Protein; D000069439:Dasatinib; C410732:PD 180970
keywords: Gap junctions; SRC; STAT3; in situ electroporation; lung cancer