Bcl-XL protein levels determine apoptotic index in pancreatic carcinoma

The present study was designed to analyze the expression of the major antiapoptotic molecules Bcl-2, Bcl-XL and the proapoptotic Bax in pancreatic ductal carcinoma and their correlation to the extent of apoptosis. Tissue samples were obtained from patients (age, 27-78 years) having surgery for pancr...

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Veröffentlicht in:Pancreas 2005-05, Vol.30 (4), p.337-342
Hauptverfasser: Sharma, Jyotika, Srinivasan, Radhika, Majumdar, Siddhartha, Mir, Snober, Radotra, Bishan Dass, Wig, Jai Dev
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container_end_page 342
container_issue 4
container_start_page 337
container_title Pancreas
container_volume 30
creator Sharma, Jyotika
Srinivasan, Radhika
Majumdar, Siddhartha
Mir, Snober
Radotra, Bishan Dass
Wig, Jai Dev
description The present study was designed to analyze the expression of the major antiapoptotic molecules Bcl-2, Bcl-XL and the proapoptotic Bax in pancreatic ductal carcinoma and their correlation to the extent of apoptosis. Tissue samples were obtained from patients (age, 27-78 years) having surgery for pancreatic cancer. Normal pancreatic tissue away from the main tumor mass was also analyzed. The levels of Bcl-2, Bcl-XL, and Bax mRNA expression were analyzed by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR). The presence of corresponding proteins was determined by immunohistochemistry (IHC). The apoptotic index was determined by terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay. A total of 25 cases were analyzed. The apoptotic index (percentage) ranged from 0.0% to 1.8%, with a median of 0.26. Semiquantitative RT-PCR revealed variable mRNA expression, with the Bcl-2/Bax ratio ranging from 0.2 to 1.5 and the Bcl-XL/Bax ratio ranging from 0.3 to 1.8. There was no correlation of mRNA levels with the apoptotic index. Immunohistochemical analysis showed positive Bcl-2, Bax, Bcl-XL expression in 20%, 72%, and 92% of cancer samples; however, their levels were variable. Spearman rank correlation coefficient test revealed a significant inverse association for the Bcl-XL IHC score and apoptotic index (P < 0.05). In contrast, Bcl-2, Bax protein levels did not show any association with the apoptotic index. However, as compared with the normal pancreas, Bcl-2, Bcl-XL, Bax were overexpressed in most of the pancreatic cancer samples (Mann-Whitney U test, P < 0.01). In pancreatic cancer, there is an upregulation of all the apoptotic regulatory molecules and the apoptotic index is chiefly determined by Bcl-XL protein levels.
doi_str_mv 10.1097/01.mpa.0000160282.64451.f1
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Tissue samples were obtained from patients (age, 27-78 years) having surgery for pancreatic cancer. Normal pancreatic tissue away from the main tumor mass was also analyzed. The levels of Bcl-2, Bcl-XL, and Bax mRNA expression were analyzed by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR). The presence of corresponding proteins was determined by immunohistochemistry (IHC). The apoptotic index was determined by terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay. A total of 25 cases were analyzed. The apoptotic index (percentage) ranged from 0.0% to 1.8%, with a median of 0.26. Semiquantitative RT-PCR revealed variable mRNA expression, with the Bcl-2/Bax ratio ranging from 0.2 to 1.5 and the Bcl-XL/Bax ratio ranging from 0.3 to 1.8. There was no correlation of mRNA levels with the apoptotic index. Immunohistochemical analysis showed positive Bcl-2, Bax, Bcl-XL expression in 20%, 72%, and 92% of cancer samples; however, their levels were variable. Spearman rank correlation coefficient test revealed a significant inverse association for the Bcl-XL IHC score and apoptotic index (P &lt; 0.05). In contrast, Bcl-2, Bax protein levels did not show any association with the apoptotic index. However, as compared with the normal pancreas, Bcl-2, Bcl-XL, Bax were overexpressed in most of the pancreatic cancer samples (Mann-Whitney U test, P &lt; 0.01). 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subjects Adult
Aged
Apoptosis
bcl-2-Associated X Protein - genetics
bcl-2-Associated X Protein - metabolism
bcl-X Protein - genetics
bcl-X Protein - metabolism
Biomarkers, Tumor - genetics
Biomarkers, Tumor - metabolism
Carcinoma, Pancreatic Ductal - metabolism
Carcinoma, Pancreatic Ductal - pathology
Female
Humans
Immunohistochemistry
In Situ Nick-End Labeling
Male
Middle Aged
Pancreatic Neoplasms - metabolism
Pancreatic Neoplasms - pathology
Proto-Oncogene Proteins c-bcl-2 - genetics
Proto-Oncogene Proteins c-bcl-2 - metabolism
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - analysis
Up-Regulation
title Bcl-XL protein levels determine apoptotic index in pancreatic carcinoma
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