KLK4T2 Is a Hormonally Regulated Transcript from the KLK4 Locus.

Area of Science:

• Molecular biology
• Genetics
• Oncology

Background:

• Human kallikrein-related peptidase 4 (KLK4) and KLKP1 are highly expressed in the prostate.
• Previous attempts to clone KLKP1 transcripts were partially unsuccessful.

Purpose of the Study:

• To investigate novel transcripts related to KLK4 and KLKP1.
• To analyze the expression patterns of KLK4, KLKP1, and the newly identified KLK4T2 in prostate cancer and benign tissues.

Main Methods:

• Identification of a novel splice variant, KLK4T2, from KLK4 and KLKP1 exons.
• Expression analysis of KLK4, KLK4T2, and KLKP1 transcripts in prostate cancer cell lines using subcellular fractionation.
• Quantitative analysis of transcript expression in patient cohorts (benign prostatic hyperplasia, primary prostate cancer, bone metastasis) and tissue panels (prostate, placenta).

Main Results:

• KLKP1 transcripts were predominantly found in the nucleus, while KLK4 and KLK4T2 were detected in the cytoplasm.
• Both KLK4T2 and KLK4 expression were significantly higher in benign prostatic hyperplasia compared to primary prostate cancer and bone metastasis.
• KLK4T2 showed highest expression in the prostate, with notable levels also found in the placenta, unlike KLK4.

Conclusions:

• KLK4T2 represents a novel androgen-regulated splice variant of KLK4.
• The distinct subcellular localization and differential expression patterns suggest a potential role for KLK4T2 in prostate health and disease.
• The predicted 17.4 kDa intracellular protein product of KLK4T2 may possess a regulatory function, warranting further investigation.