Aim: We aimed to identify defects in the programmed cell death pathway that can be related to pleural malignant mesothelioma (MM) unresponsiveness to chemotherapy. Materials and 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 resistence to oncological therapies. Therefore, Survivin may represent a promising novel target for selective therapies.
Quantitative evaluation of the apoptosis regulating genes Survivin, Bcl-2 and Bax in inflammatory and malignant pleural lesions / M. Falleni, C. Pellegrini, A. Marchetti, M. Roncalli, M. Nosotti, A. Palleschi, L. Santambrogio, G. Coggi, S. Bosari. - In: LUNG CANCER. - ISSN 0169-5002. - 48:2(2005 May), pp. 211-216.
|Titolo:||Quantitative evaluation of the apoptosis regulating genes Survivin, Bcl-2 and Bax in inflammatory and malignant pleural lesions|
FALLENI, MONICA (Primo)
COGGI, GUIDO (Penultimo)
BOSARI, SILVANO (Ultimo)
|Parole Chiave:||gene expression; survivin; Bcl-2; Bax; Bcl-2/Bax ratio; malignant mesothetioma; real-time RT-PCR|
|Settore Scientifico Disciplinare:||Settore MED/08 - Anatomia Patologica|
Settore MED/21 - Chirurgia Toracica
|Data di pubblicazione:||mag-2005|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.lungcan.2004.10.003|
|Appare nelle tipologie:||01 - Articolo su periodico|