Altered expression of tumor protein D52 regulates apoptosis and migration of prostate cancer cells.
Tumor protein D52 (TPD52) is a protein found to be overexpressed in prostate and breast cancer due to gene amplification. However, its physiological function remains under investigation. In the present study, we investigated the response of the LNCaP human prostate carcinoma cell line to deregulation of TPD52 expression. Proteomic analysis of prostate biopsies showed TPD52 overexpression at the protein level, whereas its transcriptional upregulation was demonstrated by real-time PCR. Transfection of LNCaP cells with a specific small hairpin RNA giving efficient knockdown of TPD52 resulted in significant cell death of the carcinoma LNCaP cells. As demonstrated by activation of caspases (caspase-3 and -9), and by the loss of mitochondrial membrane potential, cell death occurs due to apoptosis. The disruption of the mitochondrial membrane potential indicates that TPD52 acts upstream of the mitochondrial apoptotic reaction. To study the effect of TPD52 expression on cell proliferation, LNCaP cells were either transfected with enhanced green fluorescence protein-TPD52 or a specific small hairpin RNA. Enhanced green fluorescence protein-TPD52 overexpressing cells showed an increased proliferation rate, whereas TPD52-depleted cells showed the reverse effect. Additionally, we demonstrate that exogenous expression of TPD52 promotes cell migration via alphav beta3 integrin in prostate cancer cells through activation of the protein kinase B/Akt signaling pathway. From these results, we conclude that TPD52 plays an important role in various molecular events, particularly in the morphological diversification and dissemination of prostate carcinoma cells, and may be a promising target with respect to developing new therapeutic strategies to treat prostate cancer.
Ummanni
Ramesh
R
Department of Medical Biochemistry and Molecular Biology, University of Greifswald, Germany.
Teller
Steffen
S
Junker
Heike
H
Zimmermann
Uwe
U
Venz
Simone
S
Scharf
Christian
C
Giebel
Jürgen
J
Walther
Reinhard
R
D017209:Apoptosis / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D039302:Integrin alphaVbeta3; D008297:Male; D008928:Mitochondria / Q000502:physiology; D009363:Neoplasm Proteins / Q000235:genetics* / Q000502:physiology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction
D039302:Integrin alphaVbeta3; D009363:Neoplasm Proteins; C114751:TPD52 protein, human; D051057:Proto-Oncogene Proteins c-akt