BAD-mediated apoptotic pathway is associated with human cancer development

The malignant transformation of normal cells is caused in part by aberrant gene expression disrupting the regulation of cell proliferation, apoptosis, senescence and DNA repair. Evidence suggests that the Bcl-2 antagonist of cell death (BAD)-mediated apoptotic pathway influences cancer chemoresistan...

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Published in:International journal of molecular medicine 2015-04, Vol.35 (4), p.1081-1087
Main Authors: STICKLES, XIAOMANG B, MARCHION, DOUGLAS C, BICAKU, ELONA, SAWAH, ENTIDHAR AL, ABBASI, FOROUGH, XIONG, YIN, ZGHEIB, NADIM BOU, BOAC, BERNADETTE M, ORR, BRIAN C, JUDSON, PATRICIA L, BERRY, AMY, HAKAM, ARDESHIR, WENHAM, ROBERT M, APTE, SACHIN M, BERGLUND, ANDERS E, LANCASTER, JOHNATHAN M
Format: Article
Language:English
Subjects:
Apoptosis
Bcl-2
Breast cancer
Cancer
carcinogenesis
Chemotherapy
Colon
Colon cancer
Endometrial cancer
Gene expression
Genetic aspects
Influence
Kinases
Ovarian cancer
Phosphatase
Phosphorylation
Principal components analysis
protein phosphatase 2C
Proteins
reverse transcription quantitative-polymerase chain reaction
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Summary:The malignant transformation of normal cells is caused in part by aberrant gene expression disrupting the regulation of cell proliferation, apoptosis, senescence and DNA repair. Evidence suggests that the Bcl-2 antagonist of cell death (BAD)-mediated apoptotic pathway influences cancer chemoresistance. In the present study, we explored the role of the BAD-mediated apoptotic pathway in the development and progression of cancer. Using principal component analysis to derive a numeric score representing pathway expression, we evaluated clinico-genomic datasets (n=427) from corresponding normal, pre-invasive and invasive cancers of different types, such as ovarian, endometrial, breast and colon cancers in order to determine the associations between the BAD-mediated apoptotic pathway and cancer development. Immunofluorescence was used to compare the expression levels of phosphorylated BAD [pBAD (serine-112, -136 and -155)] in immortalized normal and invasive ovarian, colon and breast cancer cells. The expression of the BAD-mediated apoptotic pathway phosphatase, PP2C, was evaluated by RT-qPCR in the normal and ovarian cancer tissue samples. The growth-promoting effects of pBAD protein levels in the immortalized normal and cancer cells were assessed using siRNA depletion experiments with MTS assays. The expression of the BAD-mediated apoptotic pathway was associated with the development and/or progression of ovarian (n=106, p
ISSN:1107-3756
1791-244X
DOI:10.3892/ijmm.2015.2091