Analysis of androgen and anti-androgen regulation of KLK-related peptidase 2, 3, and 4 alternative transcripts in prostate cancer
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John Lai
Abstract
We assessed whether alternative transcripts (using KLK2, KLK3 and KLK4 as models) are differentially regulated by androgens and anti-androgens as an indicator of prostate cancers as they acquire treatment resistance. Using RNAseq of LNCaP cells treated with dihydrotestosterone, bicalutamide and enzalutamide, we show that the expression of variant KLK transcripts is markedly different to other variant transcripts at those loci. We also reveal that KLK variants are also over 2-fold more highly expressed in prostate cancers compared to their corresponding normal prostate. We propose that androgens and anti-androgens can activate specific variant transcripts of critical prostate cancer genes during treatment resistance.
Acknowledgments
J.A. Clements is a NHMRC Principal Research Fellow and J. Batra is a NHMRC Training Fellow. C.C. Nelson is a Queensland Government Smart Futures Premier’s Fellow. This study was funded by the Department of Health and Ageing, Australian Prostate Cancer Research Centre, Queensland, and Australian Canadian Prostate Cancer Research Alliance, a national and international research alliance program of the Queensland State Government.
Disclosure of potential conflicts of interest: No potential conflicts of interest are disclosed.
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Supplemental Material
The online version of this article (DOI: 10.1515/hsz-2014-0149) offers supplementary material, available to authorized users.
©2014 by De Gruyter
Articles in the same Issue
- Frontmatter
- Guest Editorial
- Highlight: The 5th International Symposium on Kallikreins and Kallikrein-Related Peptidases
- KLKs and their hormone-like signaling actions: a new life for the PSA-KLK family
- Putative kallikrein substrates and their (patho)biological functions
- Netherton syndrome: defective kallikrein inhibition in the skin leads to skin inflammation and allergy
- Sweetened kallikrein-related peptidases (KLKs): glycan trees as potential regulators of activation and activity
- Activation of membrane-bound proteins and receptor systems: a link between tissue kallikrein and the KLK-related peptidases
- Kallikreins are involved in an miRNA network that contributes to prostate cancer progression
- Evolution of Klk4 and enamel maturation in eutherians
- Growth and survival of lung cancer cells: regulation by kallikrein-related peptidase 6 via activation of proteinase-activated receptor 2 and the epidermal growth factor receptor
- CrataBL, a lectin and Factor Xa inhibitor, plays a role in blood coagulation and impairs thrombus formation
- Mining for single nucleotide variants (SNVs) at the kallikrein locus with predicted functional consequences
- Low mRNA expression levels of kallikrein-related peptidase 4 (KLK4) predict short-term relapse in patients with laryngeal squamous cell carcinoma
- Differential expression of multiple kallikreins in a viral model of multiple sclerosis points to unique roles in the innate and adaptive immune response
- Kallikrein-related peptidase 7 (KLK7) is a proliferative factor that is aberrantly expressed in human colon cancer
- Prognostic significance of human tissue kallikrein-related peptidases 6 and 10 in gastric cancer
- Loss of miR-378 in prostate cancer, a common regulator of KLK2 and KLK4, correlates with aggressive disease phenotype and predicts the short-term relapse of the patients
- Kallikrein-related peptidase 6 (KLK6) expression in the progression of colon adenoma to carcinoma
- Development of monoclonal antibodies to human kallikrein-related peptidase 6 (KLK6) and their use in an immunofluorometric assay for free KLK6
- Analysis of androgen and anti-androgen regulation of KLK-related peptidase 2, 3, and 4 alternative transcripts in prostate cancer
Articles in the same Issue
- Frontmatter
- Guest Editorial
- Highlight: The 5th International Symposium on Kallikreins and Kallikrein-Related Peptidases
- KLKs and their hormone-like signaling actions: a new life for the PSA-KLK family
- Putative kallikrein substrates and their (patho)biological functions
- Netherton syndrome: defective kallikrein inhibition in the skin leads to skin inflammation and allergy
- Sweetened kallikrein-related peptidases (KLKs): glycan trees as potential regulators of activation and activity
- Activation of membrane-bound proteins and receptor systems: a link between tissue kallikrein and the KLK-related peptidases
- Kallikreins are involved in an miRNA network that contributes to prostate cancer progression
- Evolution of Klk4 and enamel maturation in eutherians
- Growth and survival of lung cancer cells: regulation by kallikrein-related peptidase 6 via activation of proteinase-activated receptor 2 and the epidermal growth factor receptor
- CrataBL, a lectin and Factor Xa inhibitor, plays a role in blood coagulation and impairs thrombus formation
- Mining for single nucleotide variants (SNVs) at the kallikrein locus with predicted functional consequences
- Low mRNA expression levels of kallikrein-related peptidase 4 (KLK4) predict short-term relapse in patients with laryngeal squamous cell carcinoma
- Differential expression of multiple kallikreins in a viral model of multiple sclerosis points to unique roles in the innate and adaptive immune response
- Kallikrein-related peptidase 7 (KLK7) is a proliferative factor that is aberrantly expressed in human colon cancer
- Prognostic significance of human tissue kallikrein-related peptidases 6 and 10 in gastric cancer
- Loss of miR-378 in prostate cancer, a common regulator of KLK2 and KLK4, correlates with aggressive disease phenotype and predicts the short-term relapse of the patients
- Kallikrein-related peptidase 6 (KLK6) expression in the progression of colon adenoma to carcinoma
- Development of monoclonal antibodies to human kallikrein-related peptidase 6 (KLK6) and their use in an immunofluorometric assay for free KLK6
- Analysis of androgen and anti-androgen regulation of KLK-related peptidase 2, 3, and 4 alternative transcripts in prostate cancer
