Lundwall Åke, Ylitalo Erik Bovinder, Wikström Pernilla, Brattsand Maria
Translational Cancer Research, Department of Laboratory Medicine, Lund University, SE-223 81 Lund, Sweden.
Translational Research Center, Department of Medical Biosciences, Pathology, Umeå University, SE-901 85 Umeå, Sweden.
Int J Mol Sci. 2021 Dec 1;22(23):13023. doi: 10.3390/ijms222313023.
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.
据报道,人激肽释放酶相关肽酶4(KLK4)和转录假基因KLKP1在前列腺中高表达。在尝试克隆KLKP1的转录本时,我们部分失败了。相反,我们鉴定出一种雄激素调节的转录本KLK4T2,它似乎是KLK4的剪接变体,也包含KLKP1的外显子。前列腺癌细胞系中KLK4、KLK4T2和KLKP1转录本的表达分析显示,KLKP1转录本在细胞核和未分级细胞提取物中含量很高,而在细胞质部分几乎完全不存在。这与KLK4和KLK4T2形成对比,它们在细胞质中显示出高到中等水平。在患者队列中,我们发现与原发性前列腺癌和骨转移相比,良性前列腺增生中KLK4T2和KLK4的表达均显著更高。组织样本分析表明,KLK4T2在前列腺中表达最高,但与经典的KLK4不同,在胎盘中也发现了相对较高的水平。到目前为止,KLK4T2的功能仍有待探索,但翻译产物的结构表明它产生了一种可能具有调节功能的17.4 kDa细胞内蛋白。