TY - JOUR
AU - Yang, Cheng
AU - Fischer-Kešo, Regina
AU - Schlechter, Tanja
AU - Ströbel, Philipp
AU - Marx, Alexander
AU - Hofmann, Ilse
TI - Plakophilin 1-deficient cells upregulate SPOCK1: implications for prostate cancer progression.
JO - Tumor biology
VL - 36
IS - 12
SN - 1423-0380
CY - Berlin
PB - Springer
M1 - DKFZ-2017-03839
SP - 9567 - 9577
PY - 2015
AB - Plakophilin (PKP) 1 is frequently downregulated in prostate cancer and therefore may play a tumor-suppressive role. In the present study, we stably knocked down PKP1 in the non-neoplastic, prostatic BPH-1 cell line. In the PKP1-deficient cells, the expression of keratin 14 was lost, and the apoptosis rate was significantly reduced indicating that the cells acquired new biological capabilities. Moreover, we analyzed the gene expression profile of the PKP1-deficient BPH-1 cells. Among the genes that were significantly altered upon PKP1 knockdown, we noticed several extracellular matrix (ECM)-related genes and identified sparc/osteonectin, cwcv, and kazal-like domains proteoglycan 1 (SPOCK1/testican-1) as a gene of interest. SPOCK1 is a component of the ECM and belongs to a matricellular protein family named secreted protein, acidic, cysteine-rich (SPARC). The role of SPOCK1 in prostate cancer has not been clearly elucidated. We analyzed SPOCK1 mRNA expression levels in different cancer databases and characterized its expression in 136 prostatic adenocarcinomas by immunohistochemistry and western blot. SPOCK1 revealed a cytoplasmic localization in the glandular epithelium of the prostate and showed a significant upregulation of mRNA and protein in prostate tumor samples. Our findings support the hypothesis that PKP1 may have a tumor-suppressive function and suggest an important role of SPOCK1 in prostate tumor progression. Collectively, altered expression of PKP1 and SPOCK1 appears to be a frequent and critical event in prostate cancer.
KW - PKP1 protein, human (NLM Chemicals)
KW - Plakophilins (NLM Chemicals)
KW - Proteoglycans (NLM Chemicals)
KW - RNA, Messenger (NLM Chemicals)
KW - SPOCK1 protein, human (NLM Chemicals)
LB - PUB:(DE-HGF)16
C6 - pmid:26138584
DO - DOI:10.1007/s13277-015-3628-3
UR - https://inrepo02.dkfz.de/record/127817
ER -