BAD-mediated apoptotic pathway is associated with human cancer development
Xiaomang B Stickles1, Douglas C Marchion1, Elona Bicaku1
1Department of Women's Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
International Journal of Molecular Medicine
|February 6, 2015
Summary
The Bcl-2 antagonist of cell death (BAD)-mediated apoptotic pathway is linked to cancer development. Higher phosphorylated BAD (pBAD) levels in cancer cells promote growth, while lower PP2C phosphatase expression is observed in tumors.
Area of Science:
- Oncology
- Molecular Biology
- Cellular Biology
Background:
- Aberrant gene expression disrupts cell regulation, contributing to malignant transformation.
- The Bcl-2 antagonist of cell death (BAD)-mediated apoptotic pathway is implicated in cancer chemoresistance.
Purpose of the Study:
- To investigate the role of the BAD-mediated apoptotic pathway in cancer development and progression.
- To assess the association between BAD-mediated apoptotic pathway expression and various cancer types.
Main Methods:
- Principal component analysis of clinico-genomic datasets (n=427) from normal and cancerous tissues.
- Immunofluorescence to quantify phosphorylated BAD (pBAD) levels in normal and cancer cells.
- RT-qPCR to evaluate PP2C phosphatase expression in normal and ovarian cancer tissues.
- siRNA depletion experiments and MTS assays to assess growth effects.
Main Results:
- The BAD-mediated apoptotic pathway expression was significantly associated with ovarian, breast, colon, and endometrial cancers, and ovarian endometriosis.
- Cancer cells exhibited higher pBAD protein levels compared to normal cells.
- PP2C gene expression was lower in ovarian cancer tissues than in normal tissues.
- Depletion of PP2C led to increased pBAD levels and conferred a growth advantage to normal and cancer cells.
Conclusions:
- The BAD-mediated apoptotic pathway is associated with human cancer development.
- Elevated pBAD protein levels, potentially influenced by reduced PP2C expression, contribute to cancer cell growth and survival.
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