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Titolo:
Adenovirus-mediated Bak gene transfer induces apoptosis in mesothelioma cell lines
Autore:
Pataer, A; Smythe, WR; Yu, R; Fang, BL; McDonnell, T; Roth, JA; Swisher, SG;
Indirizzi:
Univ Texas, MD Anderson Canc Ctr, Dept Thorac & Cardiovasc Surg, Sect Thorac Mol Oncol, Houston, TX 77030 USA Univ Texas Houston TX USA 77030 t Thorac Mol Oncol, Houston, TX 77030 USA Univ Texas, MD Anderson Canc Ctr, Dept Mol Pathol, Houston, TX 77030 USA Univ Texas Houston TX USA 77030 r, Dept Mol Pathol, Houston, TX 77030 USA
Titolo Testata:
JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
fascicolo: 1, volume: 121, anno: 2001,
pagine: 61 - 67
SICI:
0022-5223(200101)121:1<61:ABGTIA>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
MALIGNANT MESOTHELIOMA; IN-VIVO; CANCER; DEATH; P53; EXPRESSION; THERAPY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
16
Recensione:
Indirizzi per estratti:
Indirizzo: Swisher, SG Univ Texas, MD Anderson Canc Ctr, Dept Thorac & Cardiovasc Surg, Sect Thorac Mol Oncol, 1515 Holcombe Blvd,Box 109, Houston, TX 77030 USAUniv Texas 1515 Holcombe Blvd,Box 109 Houston TX USA 77030 USA
Citazione:
A. Pataer et al., "Adenovirus-mediated Bak gene transfer induces apoptosis in mesothelioma cell lines", J THOR SURG, 121(1), 2001, pp. 61-67

Abstract

Objective: Conventional treatment for mesothelioma is largely ineffective. We therefore evaluated the novel approach of adenoviral gene transfer of the proapoptotic Bcl-2 family member Bak in mesothelioma cancer cell lines, which are sensitive and resistant to adenoviral p53. Methods: Binary adenoviral Bak (Ad/GT-Bak and Ad/GV16) and LacZ (Ad/GT-LacZ and Ad/GV16) vectors were used for transduction of the mesothelioma cell lines I-45 (p53 resistant) and REN (p53 sensitive). Protein levels were determined by Western blotting. Apoptosis was assessed by morphologic changes,caspase-3 cleavage, and fluorescence-activated cell sorter analysis of subdiploid populations. Cell viability was determined with the XTT assay. Statistical analysis was performed with analysis of variance and the Student t test. Results: High levels of Bak gene transfer were seen after coadministrationof Ad/GT-Bak and Ad/GV16 in both mesothelioma cell lines. Apoptosis was induced 24 hours after Bak but not LacZ gene transfer ([Bak: I-45, 36%; REN, 25%] vs [LacZ: I-45, 1%; REN, 3%], P < .05]) in p53-sensitive (REN) and p53-resistant (1-45) cell lines. Cellular viability was significantly decreased 48 to 72 hours after Bak gene transfer compared with control vector in both cell lines (72 hours: Bak 1-45, 1.4% +/- 1.0%, and Bak REN, 4.7% +/- 1%,vs Lac-Z I-45, 83% +/- 3%, and Lac-Z REN, 100% +/- 1%; P < .05). Conclusions: Adenovirus-mediated overexpression of the Bak gene induces apoptosis and decreased cellular viability in p53-sensitive and p53-resistantmesothelioma cells. These data suggest that the gene transfer of proapoptotic Bcl-2 family members may represent a novel gene therapy strategy to treat mesothelioma.

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Documento generato il 26/09/20 alle ore 14:33:49