KLK4T2 Is a Hormonally Regulated Transcript from the KLK4 Locus

Abstract

The human kallikrein-related peptidase 4 (KLK4) and the transcribed pseudogene KLKP1 are reported to be highly expressed in the prostate. When trying to clone transcripts of KLKP1, we partly failed. Instead, we identified an androgen-regulated transcript, KLK4T2, which appeared to be a splice variant of KLK4 that also contained exons of KLKP1. Expression analysis of KLK4, KLK4T2, and KLKP1 transcripts in prostate cancer cell lines showed high levels of KLKP1 transcripts in the nucleus and in unfractionated cell extract, whereas it was almost completely absent in the cytoplasmatic fraction. This was in contrast to KLK4 and KLK4T2, which displayed high to moderate levels in the cytoplasm. In patient cohorts we found significantly higher expression of both KLK4T2 and KLK4 in benign prostatic hyperplasia compared to both primary prostate cancer and bone metastasis. Analysis of tissue panels demonstrated the highest expression of KLK4T2 in the prostate, but in contrast to the classical KLK4, relatively high levels were also found in placenta. So far, the function of KLK4T2 is still to be explored, but the structure of the translation product indicated that it generates a 17.4 kDa intracellular protein with possible regulatory function.

Absence of KLK4-KLKP1 Fusion Corroborate with PTEN Loss in Characterizing Men at Higher Risk for Biochemical Recurrence in Middle Eastern Prostate Cancer Cohort

“…A group in Sweden has identi ed another androgen-regulated transcript from the same region (KLK4T2), which appears to be a splice variant of KLK4 with exons of KLKP1. In their study, they observed decreasing expression of both KLK4 and KLK4T2 from benign prostate to primary tumor to bone metastases, respectively [19].…”