Interferon Regulatory Factor 1 (IRF-1) and IRF-2 Expression in Breast Cancer Tissue Microarrays

Abstract

Interferon-gamma (IFN-gamma) is a pleiotropic cytokine with potent antitumor effects, both in vitro and in vivo. The antitumor activity of IFN-gamma is mediated in part through IFN regulatory factor-1 (IRF-1) and may be blocked by IRF-2. To test our hypothesis that some tumors escape the antitumor effects of IFN-gamma by cellular changes reflected in IRF-1 and IRF-2 expression, we examined IRF-1 and IRF-2 expression in tissue microarrays (TMA) containing 187 specimens of clinically defined invasive breast carcinoma. TMAs (Cooperative Breast Cancer Tissue Resource [CBCTR], National Cancer Institute [NCI]) were stained and then scored by three evaluators blinded to the patients' clinical status. After final scoring, the CBCTR provided the available clinical data for each patient. Whether sorted by carcinoma type or for all data together, statistical analysis showed a significant positive correlation between IRF-1 and IRF-2 expression (p = 0.01) and a negative correlation between IRF-1 expression and tumor grade (p = 0.005). IRF-1 expression is consistent with its role as a tumor suppressor; high-grade breast carcinomas were less likely to maintain expression of IRF-1, a finding consistent with a role for IRF-1 as a tumor suppressor. Further, tumors maintained expression of IRF-2 if there was coincident expression of IRF-1. These data support a model in which alterations of the expression of intracellular effectors of IFN-gamma signaling may diminish the immune-mediated tumor control mechanisms of IFN-gamma.

Tumor Suppressor Interferon-Regulatory Factor 1 Counteracts the Germinal Center Reaction Driven by a Cancer-Associated Gammaherpesvirus

“…The levels of IRF-1 protein are decreased in human leukemias and several other human cancers, supporting the role of IRF-1 as a tumor suppressor (30)(31)(32). Unfortunately, the status of IRF-1 in human lymphomas remains unexplored.…”

Involvement of IFN Regulatory Factor (IRF)-1 and IRF-2 in the Formation and Progression of Human Esophageal Cancers

“…Similarly, embryonic fibroblasts from IRF-1 knockout mice, but not wild-type mice, were transformed by forced expression of mutant c-Ha-ras oncogene (13). The loss of IRF-1 expression and gain of IRF-2 expression in human melanoma and breast cancer cells have been associated with their more malignant phenotype (14,15). In addition, incremental loss of IRF-1 expression paralleled the advancement of hepatic and endometrial cancers (16,17).…”

Intratumoral interferon regulatory factor (IRF)‐1 but not IRF‐2 is of relevance in predicting patient outcome in ovarian cancer

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