Secretogranin II is overexpressed in advanced prostate cancer and promotes the neuroendocrine differentiation of prostate cancer cells.

Abstract

AIM:

In prostate cancer (PCa), neuroendocrine differentiation (NED) is commonly observed in relapsing, hormone therapy-resistant tumours after androgen deprivation. However, the molecular mechanisms involved in the NED of PCa cells remain poorly understood. In this study, we investigated the expression of the neuroendocrine secretory protein secretogranin II (SgII) in PCa, and its potential involvement in the progression of this cancer as a granulogenic factor promoting NED.

METHODS:

We have examined SgII immunoreactivity in 25 benign prostate hyperplasia and 32 PCa biopsies. In vitro experiments were performed to investigate the involvement of SgII in the neuroendocrine differentiation and the proliferation of PCa cell lines.

RESULTS:

We showed that immunoreactive SgII intensity correlates with tumour grade in PCa patients. Using the androgen-dependent lymph node cancer prostate cells (LNCaP) cells, we found that NED triggered by androgen deprivation is associated with the induction of SgII expression. In addition, forced expression of SgII in LNCaP cells implemented a regulated secretory pathway by triggering the formation of secretory granule-like structures competent for hormone storage and regulated release. Finally, we found that SgII promotes prostate cancer (CaP) cell proliferation.

CONCLUSION:

The present data show that SgII is highly expressed in advanced PCa and may contribute to the neuroendocrine differentiation by promoting the formation of secretory granules and the proliferation of PCa cells.

• Authors: Maïté Courel, Fatima-Zohra El Yamani, David Alexandre, Hinde El Fatemi, Charlène Delestre, Maité Montero-Hadjadje, Fadl Tazi, Afaf Amarti, Rabia Magoul, Nicolas Chartrel, Youssef Anouar
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 50 Issue 17 Pg. 3039-49 (Nov 2014) ISSN: 1879-0852 [Electronic] England
• PMID: 25307750 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Androgen Antagonists
• Androgens
• Culture Media
• Neuropeptide Y
• Secretogranin II
• Steroids
• Prostate-Specific Antigen

Topics

• Androgen Antagonists (pharmacology)
• Androgens (pharmacology)
• Cell Line, Tumor
• Cell Transformation, Neoplastic (metabolism, pathology)
• Culture Media (pharmacology)
• Disease Progression
• Humans
• Male
• Neuropeptide Y (pharmacology)
• Prostate-Specific Antigen (metabolism)
• Prostatic Neoplasms (metabolism, pathology)
• Secretogranin II (metabolism)
• Steroids (pharmacology)