A possible tumor suppressor role of the KLF5 transcription factor in human breast cancer

Abstract

The 13q21 tumor suppressor locus, as defined by chromosomal deletion, harbors the KLF5 transcription factor which may have tumor suppressor function. To investigate whether KLF5 plays a role in breast cancer, we evaluated all genes and/or expressed sequence tags (ESTs) within a 3.3 Mb common region of deletion at 13q21. Of these, only KLF5 mRNA was expressed at high levels in non-neoplastic breast epithelial cells and in normal human mammary tissue, but at lower levels in various breast cancer cell lines. Using the real time TaqMan PCR assay, hemizygous deletion at KLF5 was detected in 13 out of 30, or 43% of breast cancer cell lines tested, and various degrees of loss of expression were detected in 21 out of 30, or 70% of these cell lines. Each of the cases with hemizygous deletion also exhibited loss of KLF5 expression, suggesting that loss of expression can result from chromosomal deletion, and that KLF5 may undergo haploinsufficiency during carcinogenesis. Only one of the 30 breast cancer cell lines tested exhibited a mutation in KLF5, and neither promoter methylation nor homozygous deletion was detected in any of the cell lines. In contrast, loss of heterozygosity (LOH) was frequently detected at KLF5. Re-expression of wild-type KLF5 in T-47D breast cancer cells significantly inhibited colony formation in these cells. Of the KLF5-transfected clones that did form colonies, none were found to express KLF5 mRNA. These findings suggest that loss of function by deletion and/or loss of expression frequently occurs at KLF5, and KLF5 suppresses tumor cell growth in breast cancer.