Up-regulation of gut-enriched krüppel-like factor by interferon-gamma in human colon carcinoma cells

Interferon-gamma (IFN-gamma) induces growth arrest and apoptosis of tumor cells but the mechanisms for these functions are unknown. Recently, gut-enriched krüppel-like factor (GKLF) was found to possess similar biological properties. Treatment of HT-29 cells with IFN-gamma inhibited cell proliferation and induced apoptosis, the effect was found to associate with GKLF expression. IFN-gamma stimulates GKLF mRNA and protein levels in a dose- and time-dependent manner and this process is independent of p53, occurs rapidly and does not require de novo protein synthesis indicating that GKLF is an immediate-early IFN-gamma-responsive gene. Moreover, overexpression of GKLF results in similar effect as IFN-gamma suggesting that GKLF may function as a downstream target of IFN-gamma.     

Elevated Krüppel-like factor 4 transcription factor in canine mammary carcinoma

Background

Krüppel-like factors (KLFs) are critical regulators of biological and physiological systems and have been extensively studied for their roles in cell proliferation, differentiation and survival in the context of cancer. Among the KLFs, KLF4 is highly expressed in human breast cancers and plays an oncogenic role. The present study examined the expression of KLF4 and assessed its significance in canine mammary carcinoma.

Results

Immunohistochemistry was employed to investigate the expression of KLF4 in 142 cases of canine mammary tumor. 75 of the 142 (52.8%) cases were histologically confirmed as mammary carcinoma. Quantification of immunohistochemistry was carried out using Quick score which multiply the staining intensity by the percentage of positive cells. High KLF4 expression was identified in 44 of the 75 (59%) dogs with mammary carcinoma and none in the benign cases. High KLF4 expression occurred only in the tumor cells and not the adjacent normal cells in mammary carcinoma (P < 0.001). Moreover, the high expression level of KLF4 expression was statistically associated with poor grade, late stage, histological subtypes of simple and complex carcinoma, and shorter 24-month survival. The Kaplan-Meier survival analysis also indicated that dogs with high nuclear KLF4 expression had a significantly shorter survival than those with low/moderate KLF4 expression (P = 0.011).

Conclusions

KLF4 is highly and frequently expressed in canine mammary carcinoma and correlates with a more aggressive phenotype.