Gene Expression of Kallikreins in Breast Cancer Cell Lines

Anticancer Res. 2020 May;40(5):2487-2495. doi: 10.21873/anticanres.14219.

Abstract

Background/aim: This study analyzed the gene expression of the "classic" KLK1 and "new" kallikreins KLK4-KLK15, in relation to the molecular characteristics and in vitro invasiveness of 21 breast cancer (BC) and three normal breast-derived cell lines (CLs).

Materials and methods: Gene expression of KLKs was determined by using real-time polymerase chain reaction (PCR). The invasiveness of the CLs was examined using a fibroblast-collagen-based in vitro cell culture assay.

Results: KLK5 and KLK7-KLK11 were down-regulated in several BCCLs. In contrast, KLK4, KLK8, KLK12 and KLK15 demonstrated strikingly high expression in two BCCLs, UACC 812 and MDA-MB 330. The KLK expression differed frequently according to the presence of androgen receptor (KLK1 and KLK5-KLK9), and occasionally according to estrogen receptor (KLK9) and EGFR (KLK7). Two KLK clusters were detected (first: KLK1, 4, 12, 15; second: all other KLKs), with two subclasses within the second cluster (KLK5-9 and KLK10, 11, 13, and 14). The CLs that expressed at least six KLKs belonged predominantly to basal or HER2 intrinsic subtypes. No KLK predicted the in vitro invasiveness of CLs.

Conclusion: Gene expression of KLKs was altered in BCCLs. This change was mostly down-regulation and often related to the presence of androgen receptor. The observed clusters point to a possible functional interplay of selected KLKs in BCCLs.

Keywords: Kallikreins; breast cancer; cluster analysis; gene expression; kallikrein-related peptidases.

MeSH terms

  • Biomarkers, Tumor
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Female
  • Gene Expression Profiling
  • Gene Expression*
  • Humans
  • Kallikreins / genetics*
  • Kallikreins / metabolism

Substances

  • Biomarkers, Tumor
  • Kallikreins