scholarly journals Krüppel-like factor 5 in human breast carcinoma: a potent prognostic factor induced by androgens

2012 ◽  
Vol 19 (6) ◽  
pp. 741-750 ◽  
Author(s):  
Kiyoshi Takagi ◽  
Yasuhiro Miki ◽  
Yoshiaki Onodera ◽  
Yasuhiro Nakamura ◽  
Takanori Ishida ◽  
...  

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.

2020 ◽  
Author(s):  
Lungwani Muungo

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


2006 ◽  
Vol 13 (1) ◽  
pp. 233-250 ◽  
Author(s):  
T Suzuki ◽  
S Hayashi ◽  
Y Miki ◽  
Y Nakamura ◽  
T Moriya ◽  
...  

It has been reported that agonists of peroxisome proliferator-activated receptor γ (PPARγ) inhibit proliferation of breast carcinoma cells, but the biological significance of PPARγ remains undetermined in human breast carcinomas. Therefore, we immunolocalized PPARγ in 238 human breast carcinoma tissues. PPARγ immunoreactivity was detected in 42% of carcinomas, and was significantly associated with the status of estrogen receptor (ER) α, ERβ, progesterone receptor, retinoic X receptors, p21 or p27, and negatively correlated with histological grade or cyclooxygenase-2 status. PPARγ immunoreactivity was significantly associated with an improved clinical outcome of breast carcinoma patients by univariate analysis, and multivariate analysis demonstrated that PPARγ immunoreactivity was an independent prognostic factor for overall survival in ERα-positive patients. We then examined possible mechanisms of modulation by PPARγ on estrogenic actions in MCF-7 breast carcinoma cells. A PPARγ activator, 15-deoxy-Δ12,14- prostaglandin J2 (15d-PGJ2), significantly inhibited estrogen-responsive element-dependent transactivation by estradiol in MCF-7 cells, which was blocked by addition of a PPARγ antagonist GW9662. Subsequent study, employing a custom-made microarray focused on estrogen-responsive genes, revealed that mRNA expression was significantly regulated by estradiol in 49 genes, but this significance vanished on addition of 15d-PGJ2 in 16 out of 49 (33%) genes. These findings were confirmed by real-time PCR in 11 genes. 15d-PGJ2 significantly inhibited estrogen-mediated proliferation of MCF-7 cells, and caused accumulation of p21 and p27 protein. These results suggest that PPARγ is mainly expressed in well-differentiated and ER-positive breast carcinomas, and modulates estrogenic actions.


1994 ◽  
Vol 302 (3) ◽  
pp. 649-654 ◽  
Author(s):  
Z Kiss ◽  
M Tomono ◽  
W B Anderson

The phospholipase D (PLD)-mediated synthesis of phosphatidylethanol (PtdEtOH) and the hydrolysis of phosphatidylethanolamine (PtdEtn) and phosphatidylcholine (PtdCho) were examined in drug-sensitive and multidrug-resistant lines of MCF-7 human breast carcinoma cells. In drug-sensitive (MCF-7/WT) cells, the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) failed to enhance either the synthesis of PtdEtOH or the hydrolysis of either phospholipid. In the drug-resistant (MCF-7/MDR) cells, 100 nM PMA greatly enhanced both the synthesis of PtdEtOH (approximately 21-fold) and the hydrolysis of PtdEtn (approximately 29-fold), but had no effect on the hydrolysis of PtdCho. The PLD activators sphingosine and H2O2 were found to elicit only a slight (1.28-1.4-fold) stimulatory effect on PtdCho hydrolysis in both the MCF-7/WT and MCF-7/MDR cell types, and had only a small effect on PtdEtn hydrolysis in the MCF-7/WT cells as well. However, these agents significantly (approximately 2.6-3.5-fold) stimulated PtdEtn hydrolysis in the MCF-7/MDR cells. These data indicate that MCF-7/MDR cells contain a PtdEtn-specific PLD activity which can be selectively stimulated by PMA, sphingosine and H2O2.


1989 ◽  
Vol 62 (744) ◽  
pp. 1079-1083 ◽  
Author(s):  
David E. Wazer ◽  
Oscar F. Tercilla ◽  
Peck-Sun Lin ◽  
Rupert Schmidt-Ullrich

2017 ◽  
Vol 14 (2) ◽  
pp. 2207-2217 ◽  
Author(s):  
Chu Lee ◽  
Wonjoo Chun ◽  
Rongjie Zhao ◽  
Young Dae Kim ◽  
Myung Mo Nam ◽  
...  

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