Amyloid precursor protein is a biomarker for transformed human pluripotent stem cells.
Increasing evidence suggests an important function of the β-amyloid precursor protein (APP) in malignant disease in humans; however, the biological basis for this evidence is not well understood at present. To understand the role of APP in transformed pluripotent stem cells, we studied its expression levels in human testicular germ cell tumors using patient tissues, model cell lines, and an established xenograft mouse model. In the present study, we demonstrate the cooperative expression of APP with prominent pluripotency-related genes such as Sox2, NANOG, and POU5F1 (Oct3/4). The closest homologue family member, APLP2, showed no correlation to these stem cell factors. In addition, treatment with histone deacetylase (HDAC) inhibitors suppressed the levels of APP and stem cell markers. Loss of pluripotency, either spontaneously or as a consequence of treatment with an HDAC inhibitor, was accompanied by decreased APP protein levels both in vitro and in vivo. These observations suggest that APP represents a novel and specific biomarker in human transformed pluripotent stem cells that can be selectively modulated by HDAC inhibitors.
Division of Molecular Psychiatry, Department of Psychiatry, University Medicine Goettingen, Goettingen, Germany. ramani@med.unigoettingen.de
Vivek
V
Venkataramani
Knut
K
Thiele
Carl Ludwig
CL
Behnes
Gerald G
GG
Wulf
Paul
P
Thelen
Lennart
L
Opitz
Gabriella
G
Salinas-Riester
Oliver
O
Wirths
Thomas A
TA
Bayer
Stefan
S
Schweyer
D000293:Adolescent; D000328:Adult; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D039904:Pluripotent Stem Cells / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D013736:Testicular Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014635:Valproic Acid / Q000494:pharmacology / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays; D055815:Young Adult
D016564:Amyloid beta-Protein Precursor; D014408:Biomarkers, Tumor; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D056572:Histone Deacetylase Inhibitors; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; D014635:Valproic Acid