title: Transmembrane prostatic acid phosphatase (TMPAP) interacts with snapin and deficient mice develop prostate adenocarcinoma.
abstract: The molecular mechanisms underlying prostate carcinogenesis are poorly understood. Prostatic acid phosphatase (PAP), a prostatic epithelial secretion marker, has been linked to prostate cancer since the 1930's. However, the contribution of PAP to the disease remains controversial. We have previously cloned and described two isoforms of this protein, a secretory (sPAP) and a transmembrane type-I (TMPAP). The goal in this work was to understand the physiological function of TMPAP in the prostate. We conducted histological, ultra-structural and genome-wide analyses of the prostate of our PAP-deficient mouse model (PAP(-/-)) with C57BL/6J background. The PAP(-/-) mouse prostate showed the development of slow-growing non-metastatic prostate adenocarcinoma. In order to find out the mechanism behind, we identified PAP-interacting proteins byyeast two-hybrid assays and a clear result was obtained for the interaction of PAP with snapin, a SNARE-associated protein which binds Snap25 facilitating the vesicular membrane fusion process. We confirmed this interaction by co-localization studies in TMPAP-transfected LNCaP cells (TMPAP/LNCaP cells) and in vivo FRET analyses in transient transfected LNCaP cells. The differential gene expression analyses revealed the dysregulation of the same genes known to be related to synaptic vesicular traffic. Both TMPAP and snapin were detected in isolated exosomes. Our results suggest that TMPAP is involved in endo-/exocytosis and disturbed vesicular traffic is a hallmark of prostate adenocarcinoma.
authors.affiliation: Department of Clinical Chemistry, University of Helsinki and Helsinki University Hospital Laboratory, Helsinki, Finland.
authors.forename: Ileana B
authors.initials: IB
authors.lastname: Quintero
authors.forename: Annakaisa M
authors.initials: AM
authors.lastname: Herrala
authors.forename: César L
authors.initials: CL
authors.lastname: Araujo
authors.forename: Anitta E
authors.initials: AE
authors.lastname: Pulkka
authors.forename: Sampsa
authors.initials: S
authors.lastname: Hautaniemi
authors.forename: Kristian
authors.initials: K
authors.lastname: Ovaska
authors.forename: Evgeny
authors.initials: E
authors.lastname: Pryazhnikov
authors.forename: Evgeny
authors.initials: E
authors.lastname: Kulesskiy
authors.forename: Maija K
authors.initials: MK
authors.lastname: Ruuth
authors.forename: Ylermi
authors.initials: Y
authors.lastname: Soini
authors.forename: Raija T
authors.initials: RT
authors.lastname: Sormunen
authors.forename: Leonard
authors.initials: L
authors.lastname: Khirug
authors.forename: Pirkko T
authors.initials: PT
authors.lastname: Vihko
mesh_terms: D000135:Acid Phosphatase; D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D000818:Animals; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D011485:Protein Binding; D021381:Protein Transport; D017027:Protein Tyrosine Phosphatases / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D011554:Pseudopodia / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000378:metabolism*
chemical_list: C498451:Snapin protein, mouse; D033921:Vesicular Transport Proteins; D000135:Acid Phosphatase; C428439:prostatic acid phosphatase; D017027:Protein Tyrosine Phosphatases
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