Document Detail


The milk protein α-casein functions as a tumor suppressor via activation of STAT1 signaling, effectively preventing breast cancer tumor growth and metastasis.
MedLine Citation:
PMID:  23047602     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Here, we identified the milk protein α-casein as a novel suppressor of tumor growth and metastasis. Briefly, Met-1 mammary tumor cells expressing α-casein showed a ~5-fold reduction in tumor growth and a near 10-fold decrease in experimental metastasis. To identify the molecular mechanism(s), we performed genome-wide transcriptional profiling. Interestingly, our results show that α-casein upregulates gene transcripts associated with interferon/STAT1 signaling and downregulates genes associated with "stemness." These findings were validated by immunoblot and FACS analysis, which showed the upregulation and hyperactivation of STAT1 and a decrease in the number of CD44(+) "cancer stem cells." These gene signatures were also able to predict clinical outcome in human breast cancer patients. Thus, we conclude that a lactation-based therapeutic strategy using recombinant α-casein would provide a more natural and non-toxic approach to the development of novel anticancer therapies.
Authors:
Gloria Bonuccelli; Remedios Castello-Cros; Franco Capozza; Ubaldo E Martinez-Outschoorn; Zhao Lin; Aristotelis Tsirigos; Jiao Xuanmao; Diana Whitaker-Menezes; Anthony Howell; Michael P Lisanti; Federica Sotgia
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-10-09
Journal Detail:
Title:  Cell cycle (Georgetown, Tex.)     Volume:  11     ISSN:  1551-4005     ISO Abbreviation:  Cell Cycle     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-06     Completed Date:  2013-04-23     Revised Date:  2013-11-05    
Medline Journal Info:
Nlm Unique ID:  101137841     Medline TA:  Cell Cycle     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3972-82     Citation Subset:  IM    
Affiliation:
The Jefferson Stem Cell Biology and Regenerative Medicine Center, Department of Stem Cell Biology & Regenerative Medicine, Thomas Jefferson University, Philadelphia, PA, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD44 / metabolism
Apoptosis / drug effects
Breast Neoplasms / metabolism,  pathology,  prevention & control
Caseins / metabolism,  pharmacology*
Cell Line
Cell Movement / drug effects
Cell Proliferation / drug effects
Female
Gene Expression Profiling
Humans
Interferons / metabolism
Mice
Milk, Human
Neoplastic Stem Cells / metabolism
STAT1 Transcription Factor / genetics,  metabolism*
Signal Transduction / drug effects*
Up-Regulation
Chemical
Reg. No./Substance:
0/Antigens, CD44; 0/Caseins; 0/STAT1 Transcription Factor; 0/STAT1 protein, human; 9008-11-1/Interferons
Comments/Corrections

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