title: Krüppel-like factor 5 in human breast carcinoma: a potent prognostic factor induced by androgens.
abstract: Krüppel-like factor 5 (intestinal) or Krüppel-like factor 5 (KLF5) is a zinc finger-containing transcription factor and involved in important biological processes including cell proliferation and differentiation. However, clinical significance of KLF5 protein has remained largely unknown in breast cancer. Therefore, in this study, we immunolocalized KLF5 in 113 human breast carcinoma cases. KLF5 immunoreactivity was frequently detected in the nuclei of breast carcinoma cells, and median value of the ratio of KLF5-positive carcinoma cells was 30% and was positively associated with the status of androgen receptor. KLF5 immunoreactivity was also significantly associated with increased risk of recurrence and worse clinical outcome in breast cancer patients by univariate analyses, and subsequent multivariate analyses demonstrated that KLF5 immunoreactivity was an independent prognostic factor for both disease-free and breast cancer-specific survival of the patients. We then examined possible regulation of KLF5 by androgen using MCF-7 breast carcinoma cells. KLF5 mRNA was induced by biologically active androgen 5α-dihydrotestosterone in a dose- and time-dependent manner in MCF-7 cells. In addition, results of transfection experiments demonstrated that proliferation activity of MCF-7 cells was significantly associated with the KLF5 expression level. These findings suggest that KLF5 is an androgen-responsive gene in human breast carcinomas and play important roles in the progression of breast carcinomas. KLF5 immunoreactivity is therefore considered a potent prognostic factor in human breast cancers.
authors.affiliation: Department of Pathology and Histotechnology, Tohoku University Graduate School of Medicine, Seiryo-machi, Aoba-ku, Sendai, Miyagi-ken, Japan. k-takagi@med.tohoku.ac.jp
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takagi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Miki
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Onodera
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Takanori
authors.initials: T
authors.lastname: Ishida
authors.forename: Mika
authors.initials: M
authors.lastname: Watanabe
authors.forename: Satoshi
authors.initials: S
authors.lastname: Inoue
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000728:Androgens / Q000494:pharmacology; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D013196:Dihydrotestosterone / Q000494:pharmacology; D005260:Female; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D061986:MCF-7 Cells; D008875:Middle Aged; D011379:Prognosis; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D000728:Androgens; C492214:KLF5 protein, human; D051741:Kruppel-Like Transcription Factors; D034741:RNA, Small Interfering; D013196:Dihydrotestosterone