Klf6 protein levels significantly decreased with progression in the TRAMP model of prostate cancer (P < 0.05), but there was no difference in Klf6 promoter methylation.
This study investigated the prevalence and significance of KLF6 exon 2 mutations and splice variants (SVs) in different stages of human PC progression.
In addition, a common germline polymorphism in the KLF6 gene associated with increased prostate cancer risk in a large multi-institutional study of 3411 men results in increased expression of KLF6-SV1.
This study proposes that variation at putative 8q24 cis-regulator(s) of transcription can significantly alter germline c-MYC expression levels and, thus, contribute to prostate cancer susceptibility by down-regulating the prostate tumor suppressor KLF6 gene.
Kidney and prostate cancers are leading causes of death in the world, and accumulating evidence suggests that tumor suppressor gene, Krüppel-like factor 6 (KLF6), plays an important role in both the development and the progression of cancer.
The rs3750861 affects expression of KLF6 splicing variants in prostate cancer and we found that its rare allele is associated with reduced lung cancer risk (odds ratio, 0.5; 95% CI, 0.3-0.8).
Our results do not support the suggested association of KLF6 IVS1 -27G>A germline polymorphism with pCA risk and also suggest that the variant is not a risk allele for BPH in the Finnish population.
The negative association between KLF6 IVS1-27A and prostate cancer risk supports a population-specific effect of susceptibility alleles in prostate tumorigenesis.
These include the ELAC2 (HPC2), MSR1, and RNASEL (HPC1) genes that have germline mutations in familial prostate cancer; AR, ATBF1, EPHB2 (ERK), KLF6, mitochondria DNA, p53, PTEN, and RAS that have somatic mutations in sporadic prostate cancer; AR, BRCA1, BRCA2, CHEK2 (RAD53), CYP17, CYP1B1, CYP3A4, GSTM1, GSTP1, GSTT1, PON1, SRD5A2, and VDR that have germline genetic variants associated with either hereditary and/or sporadic prostate cancer; and ANXA7 (ANX7), KLF5, NKX3-1 (NKX3.1), CDKN1B (p27), and MYC that have genomic copy number changes affecting gene function.
Here we show that a germline KLF6 single nucleotide polymorphism, confirmed in a tri-institutional study of 3,411 men, is significantly associated with an increased relative risk of prostate cancer in men, regardless of family history of disease.
Recently, high frequency (42%) of KLF6 mutations have been reported in colorectal cancers (CRC) as in prostate cancers, astrocytic gliomas and hepatocellular carcinomas.
Most recently, we identified a common KLF6 germ line single nucleotide polymorphism that is associated with an increased relative risk of prostate cancer and the increased production of three alternatively spliced, dominant-negative KLF6 isoforms.
These data indicate that acetylation may regulate KLF6 function, and its loss in some tumor-derived mutants could contribute to its failure to suppress growth in prostate cancer.
Krüppel-like factor 6 (KLF6) is a ubiquitously expressed zinc finger transcriptional factor, which has been suggested to be a candidate tumor suppressor gene in prostate cancer and astrocytic glioma.