Regulation of human tissue kallikrein-related peptidase expression by steroid hormones in 32 cell lines

Abstract

Human tissue kallikrein-related peptidases (KLK), which are secreted serine proteases, are encoded by 15 genes located on chromosome 19q13.4. Previous studies have shown that KLK expression is regulated by steroid hormones and many KLKs are dysregulated in hormone-dependent malignancies. Some KLKs are proposed biomarkers for these cancers. We have characterized KLK hormonal regulation patterns using a large number of human cell lines. KLK levels were quantified in supernatants from 32 cell lines, each subjected to four hormonal stimulations (dexamethasone, norgestrel, dihydrotestosterone or estradiol), using ELISAs. Cell lines included breast, prostate, ovarian, lung, pancreatic, colon, and cervical cancer cells, T-lymphocytes, keratinocytes and a non-cancerous epithelial breast cell line. KLKs were regulated in several cell lines not previously studied, such as keratinocytes (KLK5, 6, and 7), ovarian cancer (KLK5 and 9) and cervical cancer (KLK3, 5, 6, 7, 8, 10, 11, and 13) cells. Many KLKs were regulated by the synthetic glucocorticoid dexamethasone; specifically, KLK5, 6, 8, 10 and 11 were upregulated in several breast cancer cell lines and downregulated in several cervical cancer cell lines. Knowledge of KLK hormonal regulation patterns will help to shed further light on their potential use as biomarkers and therapeutic targets for hormone-related malignancies. © 2008 by Walter de Gruyter.