title: Sarcosine induces increase in HER2/neu expression in androgen-dependent prostate cancer cells.
abstract: Increasing evidence suggests that Human epidermal growth factor receptor 2 (HER2/neu) is involved in progression of prostate cancer. Recently, sarcosine was reported to be highly increased during prostate cancer progression, and exogenous sarcosine induces an invasive phenotype in benign prostate epithelial cells. The aim of this work was to investigate the effect of sarcosine on HER2/neu expression in prostate cancer cell lines LNCaP (androgen dependent), PC-3 and DU145 (both androgen independent). Relative amounts of HER2/neu and androgen receptor (AR) transcripts were determined using RT-qPCR. Total expression of HER2/neu was confirmed by Western blot (WB). HER2/neu protein on the surface of living LNCaP cells was visualized by confocal microscopy using a HER2/neu-specific fluorescent probe. Exposure of LNCaP cells to 50 μM sarcosine for 24 h resulted in a 58% increase of the HER2/neu mRNA level (P < 0.001) indicating that sarcosine effects HER2/neu expression on the level of transcription. Control experiments with alanine, an isomer of sarcosine, showed no significant effect on HER2/neu transcription. The upregulation of HER2/neu mRNA preceded the corresponding increment of the protein level after the 48-h exposure to sarcosine as shown by WB and confocal microscopy. Interestingly, sarcosine had no effect on the activated (phosphorylated) form of HER2/neu. No significant change in AR expression was observed after exposure to sarcosine. This is the first report indicating that sarcosine is involved in the regulation of the oncoprotein HER2/neu. Thus, sarcosine may induce prostate cancer progression by increased HER2/neu expression. However, detailed information on cellular mechanisms remains to be elucidated.
authors.affiliation: Cancer and Molecular Imaging Unit, Research Division of Clinical Biochemistry, University of Copenhagen, Koege Hospital, 4600 Koege, Denmark. mjda@regionsjaelland.dk
authors.forename: Malin
authors.initials: M
authors.lastname: Dahl
authors.forename: Pierre
authors.initials: P
authors.lastname: Bouchelouche
authors.forename: Gabriela
authors.initials: G
authors.lastname: Kramer-Marek
authors.forename: Jacek
authors.initials: J
authors.lastname: Capala
authors.forename: Jørgen
authors.initials: J
authors.lastname: Nordling
authors.forename: Kirsten
authors.initials: K
authors.lastname: Bouchelouche
mesh_terms: D000728:Androgens / Q000378:metabolism*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D012521:Sarcosine / Q000494:pharmacology*
chemical_list: D000728:Androgens; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D011944:Receptors, Androgen; D012521:Sarcosine; C410798:AR protein, human; C508053:ERBB2 protein, human