Downregulation of klotho β is associated with invasive ductal carcinoma progression.

Abstract

Klotho β (KLB) is a single-pass transmembrane protein measuring 1,043 amino acids in length that shares 41.2% homology with klotho α (KLA). KLB is a co-receptor and key regulator of the fibroblast growth factor receptor 4 (FGFR4) pathway. KLB interacts with FGFR4 to induce apoptosis and inhibit the proliferation of hepatoma cells, and KLA has been demonstrated to be a tumor suppressor in human breast cancer; however, little is known regarding the role of KLB in breast cancer. In the present study, through an immunohistochemical analysis of invasive ductal carcinoma tissue arrays, low KLB expression was identified in invasive ductal carcinoma samples compared with paired adjacent non-tumorous breast tissues (82 cases). In invasive ductal carcinoma tissues, KLB expression was negatively associated with pathological grade and lymph node metastasis. In 42 cases of paired microdissected breast specimens, the condition of the KLB gene allele was examined to determine the loss of heterozygosity (LOH), and selective LOH was identified at the KLB locus in 57.1% of primary tumors. These data suggest that KLB may be associated with the progression and metastasis of invasive ductal carcinoma, and therefore have clinical and therapeutic importance.