Interferon regulatory factor expression in human breast cancer.

Abstract

To investigate the expression of interferon regulatory factors 1 and 2 (IRF-1 and IRF-2) in human breast cancer. Interferon regulatory factors 1 and 2 are transcription factors in the interferon gamma signal transduction pathway. IRF-1 acts as the effector arm of the interferon gamma response; IRF-2 binds to the same DNA consensus sequence and opposes IRF-1 activity. Previous work in the authors' laboratory has shown the tumor suppressor activity of IRF-1 expression and the oncogenic effect of IRF-2 in human and murine tumor models, including human breast cancer cell lines. The authors' hypothesis is that this pathway is involved in human tumor development, and alterations in the expression of IRF-1 and IRF-2 may occur in breast cancer tissue compared with normal breast tissue, and between more and less differentiated breast cancers. Formalin-fixed paraffin-embedded human archival tissue specimens were obtained from 33 patients with pure ductal carcinoma in situ (DCIS) and 49 women with invasive ductal cancer. Adjacent areas of normal breast tissue were assayed in 31 women. These specimens were stained with polyclonal IRF-1 and IRF-2 antibodies using an avidin-biotin-peroxidase complex technique after epitope retrieval. Most normal breast tissue showed expression of IRF-1 and no expression of IRF-2 by immunohistochemistry. High-grade DCIS or node-positive invasive ductal cancers were less likely to express the tumor suppressor IRF-1 than normal tissue. More strikingly, high-grade DCIS and invasive ductal cancers were much more likely to express the oncogenic IRF-2 protein than was normal tissue. Expression of IRF-1 and IRF-2 is altered in human breast cancer compared with normal adjacent tissue. The loss of IRF-1 expression is consistent with tumor suppressor loss and the development of IRF-2 expression with oncogenic activation. These data support the hypothesis that this pathway is involved in human breast oncogenesis, which warrants further investigation regarding prognostic and therapeutic implications.