Comparison of positivity frequency of bcl-2 expression in prostate adenocarcinoma with low and high Gleason score

Hering, Flávio; Lipay, Mônica Vannucci Nunes; Lipay, Marco Aurélio; Rodrigues, Pedro Luiz Coelho; Nesralah, Luciano José; Srougi, Miguel

doi:10.1590/s1516-31802001000400005

Cited by 12 publications

(9 citation statements)

References 13 publications

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“…Bcl-2 overexpression is frequently found in both primary and metastatic human prostate cancers (Bauer et al, 1996;Krajewska et al, 1996). Primary tumors that overexpress Bcl-2 exhibit a high Gleason score and a high rate of cancer recurrence after radical prostatectomy (Krajewska et al, 1996;Hering et al, 2001). Following prolonged androgen ablation, chemo-or radiotherapy, Bcl-2 expression is often upregulated and associated with the development of androgen-, chemo-or radioresistance that ultimately leads to a less favorable progression (Raffo et al, 1995;Catz and Johnson, 2003;Rosser et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Overcoming the radioresistance of prostate cancer cells with a novel Bcl-2 inhibitor

Chervin

Nie

et al. 2006

Oncogene

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Bcl-2 overexpression is an important mechanism underlying the aggressive behavior of prostate cancer cells and their resistance to radio-or chemotherapy. HA14-1, a recently discovered organic Bcl-2 inhibitor, potently induces apoptosis in various human cancer cells. Sequential exposure of radioresistant LNCaP (wild-type (wt) p53), LNCaP/Bcl-2 (wt p53) and PC3 (mutant p53) prostate cancer cells to a minimally cytotoxic concentration of 10 lM HA14-1 for 1 h followed by 1-6 Gy gamma radiation, resulted in a highly synergistic (combination index o1.0) induction of cell death as determined by an apoptosis assay at 72 h, and a clonogenicity assay at 12 days, after the initial treatment. The reverse treatment sequence did not cause a synergistic induction of cell death. When compared to individual treatments, cell death induced by the combined treatment was associated with dramatically increased reactive oxygen species (ROS) generation, c-Jun N-terminal kinase (JNK) activation, Bcl-2 phosphorylation, cytochrome c release, caspase-3 activation and DNA fragmentation. Exposure to either 200 lg/ml of the antioxidant alpha-tocopherol or 10 lM JNK inhibitor SP600125 before the combined treatment resulted in decreased activation of JNK and caspase-3 as well as decreased DNA fragmentation. However, treatment with the pancaspase inhibitor carbobenzoxyl-valylalanyl-aspartyl-[O-methyl]-fluoromethylketone before the combined treatment inhibited apoptosis without affecting JNK activation, and this inhibitory effect was enhanced in the presence of alpha-tocopherol or SP600125. Taken together, our results indicate that HA14-1 potently sensitizes radioresistant LNCaP and PC3 cells to gamma radiation, regardless of the status of p53. ROS and JNK are important early signals that trigger both caspasedependent and -independent cell death pathways and contribute to the apoptotic synergy induced by the combined treatments.

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Section: Introductionmentioning

confidence: 99%

Overcoming the radioresistance of prostate cancer cells with a novel Bcl-2 inhibitor

Chervin

Nie

et al. 2006

Oncogene

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“…Expression of Bcl-2 has been described in many epithelial malignancies including that of the prostate gland 18,[25][26][27][28] . It has been confirmed that elevated levels of Bcl-2 protein can contribute to the progression of prostate cancer, to the development of metastasis, and to the hormone-insensitive stage 25,29 . The participation of Bcl-2 in multistep carcinogenesis of the prostate has been shown by in vivo experiments in transgenic mice 30 .…”

Section: Bcl-2 Familymentioning

confidence: 95%

“…Hering et al compared the frequency of positive Bcl-2 expression in adenocarcinomas of the prostate with low and high Gleason scores. They found that higher expression of Bcl-2 in tumour samples was observed in association with more advanced Gleason scores and proposed that an increase in the ratio of this antiapoptotic protein often occurs during the progression to prostate cancer 29 .…”

Section: Bcl-2 Familymentioning

confidence: 99%

The Significance of Key Regulators of Apoptosis in the Development and Prognosis of Prostate Carcinoma. I. Proteins of the BCL-2 Family and Protein P53

Knillová¹,

Kolář²

2003

BIOMED PAP

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“…Elevated levels of bcl-2 protein may contribute to the progression of prostate cancer to a metastatic and hormone-insensitive state characterized by poor responses to chemotherapy. Higher frequency of bcl-2 expression in tumor samples suggests that an increase in this anti-apoptotic protein generally occurs during PCa progression (26).…”

Section: Molecular Mechanisms In Prostate Cancer Oncogenesismentioning

confidence: 99%

Molecular aspects of prostate cancer: implications for future directions

Gimba

Barcinski

2003

Int. braz j urol.

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Many studies have been developed trying to understand the complex molecular mechanisms involved in oncogenesis and progression of prostate cancer (PCa). Current biotechnological methodologies, especially genomic studies, are adding important aspects to this area. The construction of extensive DNA sequence data and gene expression profiles have been intensively explored to search for candidate biomarkers to evaluate PCa. The use of DNA micro-array robotic systems constitutes a powerful approach to simultaneously monitor the expression of a great number of genes. The resulting gene expressing profiles can be used to specifically describe tumor staging and response to cancer therapies. Also, it is possible to follow PCa pathological properties and to identify genes that anticipate the behavior of clinical disease. The molecular pathogenesis of PCa involves many contributing factors, such as alterations in signal transduction pathways, angiogenesis, adhesion molecules expression and cell cycle control. Also, molecular studies are making clear that many genes, scattered through several different chromosomal regions probably cause predisposition to PCa. The discovery of new molecular markers for PCa is another relevant advance resulting from molecular biology studies of prostate tumors. Interesting tissue and serum markers have been reported, resulting in many cases in useful novelties to diagnostic and prognostic approaches to follow-up PCa. Finally, gene therapy comes as an important approach for therapeutic intervention in PCa. Clinical trials for PCa have been demonstrating that gene therapy is relatively safe and well tolerated, although some improvements are yet to be developed.

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Comparison of positivity frequency of bcl-2 expression in prostate adenocarcinoma with low and high Gleason score

Abstract: The higher frequency of bcl-2 immunostaining in tumor samples was observed in association with more advanced Gleason scores and suggests that an increase in the ratio of this anti-apoptotic protein often occurs during progression of prostate cancers.

Cited by 12 publications

References 13 publications

Overcoming the radioresistance of prostate cancer cells with a novel Bcl-2 inhibitor

Overcoming the radioresistance of prostate cancer cells with a novel Bcl-2 inhibitor

The Significance of Key Regulators of Apoptosis in the Development and Prognosis of Prostate Carcinoma. I. Proteins of the BCL-2 Family and Protein P53

Molecular aspects of prostate cancer: implications for future directions

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