Deletion, mutation, and loss of expression of KLF6 in human prostate cancer.
Kruppel-like factors (KLFs) are a group of transcription factors that appear to be involved in different biological processes including carcinogenesis. In a recent study, KLF6 was reported as a tumor suppressor gene in prostate cancer because of its frequent loss of heterozygosity (LOH) and mutation as well as functional suppression of cell proliferation. Loss of chromosomal locus spanning KLF6 is relatively infrequent in other published studies of prostate cancer, however. To clarify the role of KLF6 in prostate cancers, particularly those that are high grade, we examined KLF6 for deletion, mutation, and loss of expression in 96 prostate cancer samples including 21 xenografts/cell lines. Loss of heterozygosity occurred in 4 (19%) of 21 xenografts/cell lines and 8 (28%) of 29 informative tumors. Fourteen of the 96 (15%) samples showed 15 somatic sequence changes in the KLF6 gene, including 7 that changed KLF6 peptide sequences, 4 that did not, and 4 that were located in untranslated regions. Expression levels of KLF6 were significantly lost in 4 of 20 (20%) xenografts/cell lines of prostate cancer, as detected by RT-PCR and Northern blot analysis. These findings indicate that significant genetic alterations of KLF6 occur in a minority of high-grade prostate cancers.
Chen
Ceshi
C
Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia, USA.
Hyytinen
Eija-Riitta
ER
Sun
Xiaodong
X
Helin
Heikki J
HJ
Koivisto
Pasi A
PA
Frierson
Henry F
HF
Vessella
Robert L
RL
Dong
Jin-Tang
JT
D020121:5' Untranslated Regions / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D005091:Exons; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors; D019656:Loss of Heterozygosity; D008297:Male; D051379:Mice; D009154:Mutation; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D011518:Proto-Oncogene Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D020121:5' Untranslated Regions; D017931:DNA Primers; C105465:KLF6 protein, human; C491358:Klf6 protein, mouse; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators