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RUNX1 and its understudied role in breast cancer.

ABSTRACT: The transcription factor Runt-related transcription factor 1 (RUNX1) is critical for the earliest steps of hematopoiesis. RUNX1 was originally identified as a gene fusion in acute myeloid leukemia (AML) and thus has garnered heavy attention as a tumor suppressor in hematopoietic malignancies. However, RUNX1 is also strongly expressed in breast epithelia and may be misregulated during tumorigenesis. Here, I discuss our recent work implicating RUNX1 in proliferation control during breast epithelial-acinar morphogenesis. My goal is to place these findings in the context of a handful of other reports, which together argue that RUNX1 could act as a tumor suppressor gene in breast cancer. Testing this hypothesis requires focused in vivo studies, because the major commercial platform for global mRNA expression profiling does not reliably reflect RUNX1 levels. Our in vitro results indicate that hyperproliferation in RUNX1-deficient breast epithelia relies on another family of transcription factors, the Forkhead box O (FOXO) proteins. FOXOs could, therefore, represent a synthetic-lethal target for RUNX1-deficient tumors if the hypothesized link to breast cancer is correct.

SUBMITTER: Janes KA

PROVIDER: S-EPMC3266176 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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RUNX1 and its understudied role in breast cancer.

Janes Kevin A KA

Cell cycle (Georgetown, Tex.) 20111015 20

The transcription factor Runt-related transcription factor 1 (RUNX1) is critical for the earliest steps of hematopoiesis. RUNX1 was originally identified as a gene fusion in acute myeloid leukemia (AML) and thus has garnered heavy attention as a tumor suppressor in hematopoietic malignancies. However, RUNX1 is also strongly expressed in breast epithelia and may be misregulated during tumorigenesis. Here, I discuss our recent work implicating RUNX1 in proliferation control during breast epithelia ...[more]

PMID: 22024923

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Project description:BackgroundAlthough evidence linking environmental chemicals to breast cancer is growing, mixtures-based exposure evaluations are lacking.ObjectiveThis study aimed to identify environmental chemicals in use inventories that co-occur and share properties with chemicals that have association with breast cancer, highlighting exposure combinations that may alter disease risk.MethodsThe occurrence of chemicals within chemical use categories was characterized using the Chemical and Products Database. Co-exposure patterns were evaluated for chemicals that have an association with breast cancer (BC), no known association (NBC), and understudied chemicals (UC) identified through query of the Silent Spring Institute's Mammary Carcinogens Review Database and the U.S. Environmental Protection Agency's Toxicity Reference Database. UCs were ranked based on structure and physicochemical similarities and co-occurrence patterns with BCs within environmentally relevant exposure sources.ResultsA total of 6793 chemicals had data available for exposure source occurrence analyses. 50 top-ranking UCs spanning five clusters of co-occurring chemicals were prioritized, based on shared properties with co-occuring BCs, including chemicals used in food production and consumer/personal care products, as well as potential endocrine system modulators.SignificanceResults highlight important co-exposure conditions that are likely prevalent within our everyday environments that warrant further evaluation for possible breast cancer risk.Impact statementMost environmental studies on breast cancer have focused on evaluating relationships between individual, well-known chemicals and breast cancer risk. This study set out to expand this research field by identifying understudied chemicals and mixtures that may occur in everyday environments due to their patterns of commercial use. Analyses focused on those that co-occur alongside chemicals associated with breast cancer, based upon in silico chemical database querying and analysis. Particularly in instances when understudied chemicals share physicochemical properties and structural features with carcinogens, these chemical mixtures represent conditions that should be studied in future clinical, epidemiological, and toxicological studies.

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RUNX1 and its understudied role in breast cancer.

Publications

RUNX1 and its understudied role in breast cancer.

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