Journal article
Regulator of G Protein Signaling 6 (RGS6) Induces Apoptosis in Mammary Tumor Cells via a Mitochondrial‐dependent Pathway Not Involving Its GTPase‐Activating Protein Activity
The FASEB journal, Vol.25, pp.751.7-751.7
04/2011
DOI: 10.1096/fasebj.25.1_supplement.751.7
Abstract
RGS6 is a member of the RGS family of proteins that function as GTPase‐activating proteins (GAPs) for Gá subunits. Given the role of RGS6 as a G protein GAP, the link between G protein activation and cancer, and a reduced cancer risk in humans expressing an RGS6 SNP leading to its increased translation, we hypothesized that RGS6 functions to inhibit cancer cell growth. We found a marked down‐regulation of RGS6 in human mammary ductal epithelial cells during their transformation that correlates with disease progression. RGS6 exhibited impressive anti‐proliferative actions in breast cancer cells, including inhibition of cell growth and colony formation and induction of cell cycle arrest and apoptosis by p53‐independent mechanisms. RGS6 activated the intrinsic pathway of apoptosis involving regulation of Bax/Bcl‐2, cytochrome C release, and activation of caspases‐3 and ‐9. It also promoted loss of mitochondrial membrane potential and increases in reactive oxygen species, the latter functioning in a feed‐forward amplification path to induce apoptosis and cell death. RGS6 loss dramatically impaired doxorubicin‐induced growth suppression and apoptosis in MEFs. Surprisingly, RGS6 induced apoptosis independent of its GAP activity. This work demonstrates a novel signaling action of RGS6 in cell death pathways and identifies RGS6 as a possible therapeutic target for breast cancer. (NIH GM075033, GM075033‐03S1).
Details
- Title: Subtitle
- Regulator of G Protein Signaling 6 (RGS6) Induces Apoptosis in Mammary Tumor Cells via a Mitochondrial‐dependent Pathway Not Involving Its GTPase‐Activating Protein Activity
- Creators
- Biswanath MaityJianqi Yang - University of Iowa, Neuroscience and PharmacologyJie Huang - University of IowaRyan W Askeland - University of Iowa Carver College of MedicineRory A Fisher - University of Iowa, Neuroscience and Pharmacology
- Resource Type
- Journal article
- Publication Details
- The FASEB journal, Vol.25, pp.751.7-751.7
- Publisher
- Federation of American Societies for Experimental Biology
- DOI
- 10.1096/fasebj.25.1_supplement.751.7
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Number of pages
- 1
- Language
- English
- Date published
- 04/2011
- Academic Unit
- Neuroscience and Pharmacology; Internal Medicine; Iowa Neuroscience Institute
- Record Identifier
- 9984071644802771
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