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EGR1 is a direct target of KLF12 mediating cell viability.

(A) Chromatin immunoprecipitation (ChIP) assay showed binding of KLF12 to motif 2 of the EGR1 promoter, but not to motif 1 in LS-174T cells. Immunoprecipitation with IgG antibody was used as a control. (B) Transient co-transfection of cells was performed with EGR1 promoter wild type (WT), or mutant luciferase reporter plasmids with renilla luciferase control plasmids and non-targeting or KLF12 siRNA. The luciferase activity was determined. (C) EGR1 protein levels in CRC cell lines. Actin served as a loading control. (D) EGR1 mRNA (left) and protein (right) levels in LS174T cells stably transfected with either GFP or KLF12. Actin served as a loading control. E. EGR1 mRNA (left) and protein (right) levels in HCT116 cells stably transfected with either a vector containing nonsilencing control shRNA (shCon) or one of two KLF12 shRNAs (shKLF12-1 and shKLF12-2). Actin served as a loading control.</p

KLF12 and EGR1 expression levels are synergistically correlated with worse prognosis in CRC.

<p>Kaplan-Meier Disease free survival (DFS) curves of a cohort of 232 CRC patients (Moffitt cohort, n = 177; Vanderbilt Medical Center cohort, n = 55) with either high or low mRNA levels of KLF12 (A), EGR1 (B), or both (C). Vertical bars denote censored patients.</p

KLF12 promotes tumor growth <i>in vitro</i> and <i>in vivo</i>.

<p>(A) KLF12 protein levels in CRC cell lines. Actin served as a loading control. (B) KLF12 expression (top) and cell viability (bottom) of LS174T cells stably transfected with either GFP or KLF12. Actin served as a loading control. C. KLF12 expression (top) and cell viability (bottom) of HCT116 cells stably transfected with either a vector containing nonsilencing control shRNA (shCon) or one of two KLF12 shRNAs (shKLF12-1 and shKLF12-2). Actin served as a loading control. D. Tumor weight in mice orthotopically injected with either LS174T/GFP or LS174T/KLF12 cells (n = 8 for each group). E. Tumor weight in mice orthotopically injected with either HCT116/shCon, HCT116/shKLF12-1, or HCT116/shKLF12-2 cells (n = 9 for each group).</p

KLF12 enhances cell viability by activating EGR1.

<p>(A) Protein levels of KLF12 and EGR1 (left) and cell viability (right) of LS174T/GFP and LS174T/KLF12 cells transfected with either non-targeting siRNA as control (con) or EGR1 siRNA. Actin served as a loading control. (B) EGR1 protein levels (left) and cell viability (right) of LS174T cells transfected with either GFP (LS174T/GFP) or EGR1 (LS174T/EGR1). (C) Tumor weight in mice orthotopically injected with either LS174T/GFP or LS174T/EGR1 cells (n = 8 for each group).</p

Krüppel-Like Factor 12 Promotes Colorectal Cancer Growth through Early Growth Response Protein 1

<div><p>Krüppel-like factor 12 (KLF12) is a transcription factor that plays a role in normal kidney development and repression of decidualization. KLF12 is frequently elevated in esophageal adenocarcinoma and has been reported to promote gastric cancer progression. Here, we examined the role of KLF12 in colorectal cancer (CRC). Indeed, KLF12 promotes tumor growth by directly activating early growth response protein 1 (EGR1). The levels of KLF12 and EGR1 correlate synergistically with a poor prognosis. These results indicate that KLF12 likely plays an important role in CRC and could serve as a potential prognostic marker and therapeutic target.</p></div

KLF12 and EGR1 is co-expressed <i>in vivo</i>.

<p>(A) Immunohistochemistry of EGR1 in nude mice injected with either LS174/GFP cells as control, or with LS174 cells stably transfected with KLF12 (LS174/KLF12). (B) Immunohistochemistry of KLF12 and EGR1 in matching sections taken from two CRC patients (Patient #1 and #2). Magnification x10. (C) Pearson correlation of KLF12 and EGR1 mRNA expression in a cohort of 232 CRC patients (Moffitt cohort, n = 177 and Vanderbilt Medical Center cohort, n = 55).</p