Journal article
Androgen deprivation induces human prostate epithelial neuroendocrine differentiation of androgen-sensitive LNCaP cells
Endocrine-related cancer, Vol.13(1), pp.151-167
03/2006
DOI: 10.1677/erc.1.01043
PMID: 16601285
Abstract
Neuroendocrine (NE) cells are the minor cell populations in normal prostate epithelial compartments. During prostate carcinogenesis, the number of NE cells in malignant lesions increases, correlating with its tumorigenicity and hormone-refractory growth. It is thus proposed that cancerous NE cells promote prostate cancer (PCa) cell progression and its androgen-independent proliferation, although the origin of the cancerous NE cells is not clear. To investigate the role of cancerous NE cells in prostate carcinogenesis, we characterized three NE subclone cell lines-NE-1.3, NE-1.8 and NE-1.9, which were transdifferentiated from androgen-sensitive human PCa LNCaP cells by culturing in an androgen-depleted environment, resembling clinical androgen-ablation therapy. These subclone cells acquire many features of NE cells seen in clinical prostate carcinomas, for example exhibiting a neuronal morphology and expressing multiple NE markers, including neuron-specific enolase, chromogranin B, neurotensin, parathyroid hormone-related peptide, and to a lesser degree for chromogranin A, while lacking androgen receptor (AR) or prostate specific antigen (PSA) expression. These cells represent terminally differentiated stable cells because after 3 months of re-culturing in a medium containing androgenic activity, they still retained the NE phenotype and expressed NE markers. Despite these NE cells having a slow growth rate, they readily developed xenograft tumors. Furthermore, media conditioned by these NE cells exhibited a stimulatory effect on proliferation and PSA secretion by LNCaP cells in androgen-deprived conditions. Additionally, we found that receptor protein tyrosine phosphatase alpha plays a role in upregulating multiple NE markers and acquiring the NE phenotype. These NE cells thus represent cancerous NE cells and could serve as a useful cell model system for investigating the role of cancerous NE cells in hormone-refractory proliferation of PCa cells.
Details
- Title: Subtitle
- Androgen deprivation induces human prostate epithelial neuroendocrine differentiation of androgen-sensitive LNCaP cells
- Creators
- Ta-Chun Yuan - University of Nebraska Medical CenterSuresh Veeramani - University of Nebraska Medical CenterFen-Fen Lin - University of Nebraska Medical CenterDmitry Kondrikou - University of Nebraska Medical CenterStanislav Zelivianski - University of Nebraska Medical CenterTsukasa Igawa - Nagasaki UniversityDev Karan - University of Nebraska Medical CenterSurinder K Batra - Biochemistry & Molecular BiologyMing-Fong Lin - Biochemistry & Molecular Biology
- Resource Type
- Journal article
- Publication Details
- Endocrine-related cancer, Vol.13(1), pp.151-167
- DOI
- 10.1677/erc.1.01043
- PMID
- 16601285
- ISSN
- 1351-0088
- eISSN
- 1479-6821
- Grant note
- P20 RR 017675 / NCRR NIH HHS P20 RR 018759 / NCRR NIH HHS CA 88184 / NCI NIH HHS
- Language
- English
- Date published
- 03/2006
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984359929602771
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