title: Quantitative evaluation of the apoptosis regulating genes Survivin, Bcl-2 and Bax in inflammatory and malignant pleural lesions.
abstract: OBJECTIVE
  We aimed to identify defects in the programmed cell death pathway that can be related to pleural malignant mesothelioma (MM) unresponsiveness to chemotherapy.
  
  
  METHODS
  We quantified mRNA levels of the apoptosis regulating genes Survivin, member of the IAP family, Bcl-2 and Bax, members of the Bcl-2 family. We studied 22 non-neoplastic pleural samples, comprising normal and inflammatory tissue specimens, and 42 pleural MMs using real-time RT-PCR.
  
  
  RESULTS
  Very low mRNA levels of each apoptotic gene were detected in all normal pleural samples. All three genes displayed increased mRNA levels in inflammatory and tumor specimens. Survivin levels in pleuritis and MMs were significantly increased (333% and 908%, respectively) compared to normal counterparts (p=0.0147 and 0.00349, respectively). Bcl-2 and Bax levels were increased in inflammatory pleural samples (394%, p=0.001 and 188%, p=ns, respectively) and in MMs (94%, p=ns and 88%, p=0.0163, respectively). The Bcl-2/Bax ratio was higher in pleuritis than in MMs, compared to normal pleurae (441%, p=ns and 22%, p=ns, respectively); the difference between Bcl-2/Bax ratio in inflammatory and neoplastic pleural samples was significant (p=0.00375).
  
  
  CONCLUSIONS
  These results suggest that apoptotic defects in pleural MMs are linked to increased levels of Survivin, whereas variations in Bcl-2 and Bax expression appear less significant, although further studies are needed to highlight Bcl-2 family members interactions in apoptosis control. Survivin progressive accumulation from normal pleura to MM suggests this gene may be important in mesothelial cancerogenesis. Survivin overexpression may also be involved in pleural MM resistance to oncological therapies. Therefore, Survivin may represent a promising novel target for selective therapies.
authors.affiliation: Department of Medicine Surgery and Dentistry, Division of Pathology, University of Milan, AO San Paolo e IRCCS Ospedale Maggiore, Via A. Di Rudinì 8, 20142 Milan, Italy. monica.falleni@unimi.it
authors.forename: Monica
authors.initials: M
authors.lastname: Falleni
authors.forename: Caterina
authors.initials: C
authors.lastname: Pellegrini
authors.forename: Antonio
authors.initials: A
authors.lastname: Marchetti
authors.forename: Massimo
authors.initials: M
authors.lastname: Roncalli
authors.forename: Mario
authors.initials: M
authors.lastname: Nosotti
authors.forename: Alessandro
authors.initials: A
authors.lastname: Palleschi
authors.forename: Luigi
authors.initials: L
authors.lastname: Santambrogio
authors.forename: Guido
authors.initials: G
authors.lastname: Coggi
authors.forename: Silvano
authors.initials: S
authors.lastname: Bosari
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000235:genetics*; D016022:Case-Control Studies; D002471:Cell Transformation, Neoplastic; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D019254:Genes, bcl-2; D006801:Humans; D007249:Inflammation; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology*; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009363:Neoplasm Proteins; D010995:Pleural Diseases / Q000235:genetics / Q000503:physiopathology; D010997:Pleural Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077022:Survivin; D051028:bcl-2-Associated X Protein
chemical_list: D000970:Antineoplastic Agents; C494826:BAX protein, human; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D000077022:Survivin; D051028:bcl-2-Associated X Protein