Transmembrane prostatic acid phosphatase (TMPAP) interacts with snapin and deficient mice develop prostate adenocarcinoma

Ileana B Quintero; Annakaisa M Herrala; César L Araujo; Anitta E Pulkka; Sampsa Hautaniemi; Kristian Ovaska; Evgeny Pryazhnikov; Evgeny Kulesskiy; Maija K Ruuth; Ylermi Soini; Raija T Sormunen; Leonard Khirug; Pirkko T Vihko

doi:10.1371/journal.pone.0073072

Transmembrane prostatic acid phosphatase (TMPAP) interacts with snapin and deficient mice develop prostate adenocarcinoma

PLoS One. 2013 Sep 10;8(9):e73072. doi: 10.1371/journal.pone.0073072. eCollection 2013.

Authors

Ileana B Quintero¹, Annakaisa M Herrala, César L Araujo, Anitta E Pulkka, Sampsa Hautaniemi, Kristian Ovaska, Evgeny Pryazhnikov, Evgeny Kulesskiy, Maija K Ruuth, Ylermi Soini, Raija T Sormunen, Leonard Khirug, Pirkko T Vihko

Affiliation

¹ Department of Clinical Chemistry, University of Helsinki and Helsinki University Hospital Laboratory, Helsinki, Finland.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acid Phosphatase
Adenocarcinoma / genetics*
Adenocarcinoma / metabolism*
Adenocarcinoma / pathology
Adenocarcinoma / ultrastructure
Animals
Cell Line, Tumor
Cell Transformation, Neoplastic / genetics
Disease Models, Animal
Male
Mice
Mice, Knockout
Models, Biological
Prostate / metabolism
Prostate / pathology
Prostatic Neoplasms / genetics*
Prostatic Neoplasms / metabolism*
Prostatic Neoplasms / pathology
Prostatic Neoplasms / ultrastructure
Protein Binding
Protein Transport
Protein Tyrosine Phosphatases / deficiency
Protein Tyrosine Phosphatases / genetics*
Protein Tyrosine Phosphatases / metabolism*
Pseudopodia / metabolism
Vesicular Transport Proteins / metabolism*

Substances

Snapin protein, mouse
Vesicular Transport Proteins
Acid Phosphatase
prostatic acid phosphatase
Protein Tyrosine Phosphatases

Grants and funding

This work was supported by grants from the Academy of Finland to P.V. (grant no. 132201) and to Center of Excellence in Cancer Genetics (S.H., K.O.); and The Sigrid Jusélius Foundation grants to P.V., and to S.H. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.