Kru¨ ppel-like factor 5 in human breast carcinoma: a potent prognostic factor induced by androgens

Kru¨ ppel-like factor 5 (intestinal) or Kru¨ ppel-like factor 5 (KLF5) is a zinc finger-containingtranscription factor and involved in important biological processes including cell proliferation anddifferentiation. However, clinical significance of KLF5 protein has remained largely unknown inbreast cancer. Therefore, in this study, we immunolocalized KLF5 in 113 human breast carcinomacases. KLF5 immunoreactivity was frequently detected in the nuclei of breast carcinoma cells, andmedian value of the ratio of KLF5-positive carcinoma cells was 30% and was positively associatedwith the status of androgen receptor. KLF5 immunoreactivity was also significantly associated withincreased risk of recurrence and worse clinical outcome in breast cancer patients by univariateanalyses, and subsequent multivariate analyses demonstrated that KLF5 immunoreactivity was anindependent prognostic factor for both disease-free and breast cancer-specific survival of thepatients. We then examined possible regulation of KLF5 by androgen using MCF-7 breastcarcinoma cells. KLF5 mRNA was induced by biologically active androgen 5a-dihydrotestosteronein a dose- and time-dependent manner in MCF-7 cells. In addition, results of transfectionexperiments demonstrated that proliferation activity of MCF-7 cells was significantly associatedwith the KLF5 expression level. These findings suggest that KLF5 is an androgen-responsive genein humanbreast carcinomas and play important roles in the progression of breast carcinomas. KLF5immunoreactivity is therefore considered a potent prognostic factor in human breast cancers.Endocrine-Related Cancer (2012) 19 741–750