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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Buchner, Johannes / Ludwig, Stephan / Sies, Helmut / Turk, Boris / Wittinghofer, Alfred

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

Julie L.V. Shaw1 / Eleftherios P. Diamandis2

1Department of Pathology and Laboratory Medicine and Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto M5T 3L9, ON, Canada and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto M5T 3L9, ON, Canada

2Department of Pathology and Laboratory Medicine and Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto M5T 3L9, ON, Canada and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto M5T 3L9, ON, Canada

Corresponding author

Citation Information: Biological Chemistry. Volume 389, Issue 11, Pages 1409–1419, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: 10.1515/BC.2008.158, September 2008

Publication History

Received:
2008-02-21
Accepted:
2008-07-23
Published Online:
2008-09-11

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.

Keywords: cancer biomarkers; cell lines; gene regulation; kallikrein-related peptidases; serine proteases; steroid hormones

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