title: p63 and p73 isoform expression in non-small cell lung cancer and corresponding morphological normal lung tissue.
abstract: BACKGROUND
  The TP73 and TP63 genes are members of the p53 tumor suppressor family and are expressed in different N-terminal isoforms either with proapoptotic (transactivation domain, TA) and antiapoptotic (N-terminally truncated, ΔN) function. Unlike p53, the role of p73 and p63 in tumor is controversial. It has been recently hypothesized that altered ΔN:TA expression ratio, rather than single isoform overexpression, plays a role in the pathogenesis of many diseases, including lung cancer.
  
  
  METHODS
  Isoform-specific, real-time polymerase chain reaction and immunohistochemistry analysis on matched cancer and corresponding normal tissues from surgically resected non-small cell lung cancers (NSCLCs) have been performed aiming to explore the expression levels of each p63 and p73 N-terminal isoforms and their ΔN:TA expression ratio.
  
  
  RESULTS
  For both p63 and p73, a N-terminal isoform-specific modulation that alter ΔN:TA isoform balance was identified. In particular, ΔNp63 isoform was significantly up-modulated, whereas TAp63 was slightly down-modulated in NSCLC specimens. Likewise, Δ2p73 and Δ2/3p73 were up-modulated, whereas ΔNp73 and ΔN'p73 isoforms were down-modulated. Moreover, a higher TAp63 and ΔN'p73 transcripts expression, detected in the normal tissue surrounding the tumors, correlates with poor patient outcome, representing independent prognostic factors for overall survival (ΔN'p73: p = 0.049, hazard ratio = 3.091, 95% confidence interval = 1.005-9.524 and TAp63: p = 0.001, hazard ratio = 8.091, 95% confidence interval = 2.254-29.05).
  
  
  CONCLUSIONS
  Our findings suggest that p63 and p73 altered ΔN:TA expression ratio occurs in NSCLC likely contributing to the molecular pathogenesis of this tumor.
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin, Turin, Italy. marco.loiacono@unito.it
authors.forename: Marco
authors.initials: M
authors.lastname: Lo Iacono
authors.forename: Valentina
authors.initials: V
authors.lastname: Monica
authors.forename: Silvia
authors.initials: S
authors.lastname: Saviozzi
authors.forename: Paolo
authors.initials: P
authors.lastname: Ceppi
authors.forename: Enrico
authors.initials: E
authors.lastname: Bracco
authors.forename: Mauro
authors.initials: M
authors.lastname: Papotti
authors.forename: Giorgio V
authors.initials: GV
authors.lastname: Scagliotti
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018287:Carcinoma, Large Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008168:Lung / Q000378:metabolism*; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism*; D011379:Prognosis; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism*; D014157:Transcription Factors; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; C115051:TP63 protein, human; C000606460:TP73 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; C000606369:delta Np73 protein, human