Androgen deprivation induces human prostate epithelial neuroendocrine differentiation of androgen-sensitive LNCaP cells.

2.50
Hdl Handle:
http://hdl.handle.net/10146/59373
Title:
Androgen deprivation induces human prostate epithelial neuroendocrine differentiation of androgen-sensitive LNCaP cells.
Authors:
Yuan, Ta-Chun; Veeramani, Suresh; Lin, Fen-Fen; Kondrikou, Dmitry; Zelivianski, Stanislav; Igawa, Tsukasa; Karan, Dev; Batra, Surinder K.; Lin, Ming-Fong
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.
Citation:
Endocr. Relat. Cancer 2006, 13 (1):151-167
Journal:
Endocrine-related cancer
Issue Date:
Mar-2006
URI:
http://hdl.handle.net/10146/59373
DOI:
10.1677/erc.1.01043
PubMed ID:
16601285
Additional Links:
http://erc.endocrinology-journals.org/cgi/content/full/13/1/151
Type:
Article
Language:
en
Description:
KEYWORDS CLASSIFICATION: Adenocarcinoma;Androgens;Animals;Biology;Cell Differentiation;Chromogranin A;Chromogranins;Epithelial Cells;Humans;metabolism;Male;mechanisms of carcinogenesis;Mice;Mice,Inbred BALB C;Mice,Nude;Molecular Biology;Neurotensin;pathology;physiology;Parathyroid Hormone-Related Protein;Phosphopyruvate Hydratase;Prostate-Specific Antigen;Prostatic Neoplasms;Protein-Tyrosine-Phosphatase;Receptors,Androgen;Receptors,Cell Surface;Research;secretion;therapy;Tumor Cells,Cultured.
ISSN:
1351-0088
Appears in Collections:
Articles with annotation

Full metadata record

DC FieldValue Language
dc.contributor.authorYuan, Ta-Chun-
dc.contributor.authorVeeramani, Suresh-
dc.contributor.authorLin, Fen-Fen-
dc.contributor.authorKondrikou, Dmitry-
dc.contributor.authorZelivianski, Stanislav-
dc.contributor.authorIgawa, Tsukasa-
dc.contributor.authorKaran, Dev-
dc.contributor.authorBatra, Surinder K.-
dc.contributor.authorLin, Ming-Fong-
dc.date.accessioned2009-04-03T07:57:35Z-
dc.date.available2009-04-03T07:57:35Z-
dc.date.issued2006-03-
dc.identifier.citationEndocr. Relat. Cancer 2006, 13 (1):151-167en
dc.identifier.issn1351-0088-
dc.identifier.pmid16601285-
dc.identifier.doi10.1677/erc.1.01043-
dc.identifier.urihttp://hdl.handle.net/10146/59373-
dc.descriptionKEYWORDS CLASSIFICATION: Adenocarcinoma;Androgens;Animals;Biology;Cell Differentiation;Chromogranin A;Chromogranins;Epithelial Cells;Humans;metabolism;Male;mechanisms of carcinogenesis;Mice;Mice,Inbred BALB C;Mice,Nude;Molecular Biology;Neurotensin;pathology;physiology;Parathyroid Hormone-Related Protein;Phosphopyruvate Hydratase;Prostate-Specific Antigen;Prostatic Neoplasms;Protein-Tyrosine-Phosphatase;Receptors,Androgen;Receptors,Cell Surface;Research;secretion;therapy;Tumor Cells,Cultured.en
dc.description.abstractNeuroendocrine (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.en
dc.language.isoenen
dc.relation.urlhttp://erc.endocrinology-journals.org/cgi/content/full/13/1/151en
dc.subject.meshAdenocarcinoma-
dc.subject.meshAndrogens-
dc.subject.meshAnimals-
dc.subject.meshCell Differentiation-
dc.subject.meshChromogranin A-
dc.subject.meshChromogranins-
dc.subject.meshEpithelial Cells-
dc.subject.meshHumans-
dc.subject.meshMale-
dc.subject.meshMice-
dc.subject.meshMice, Inbred BALB C-
dc.subject.meshMice, Nude-
dc.subject.meshNeurotensin-
dc.subject.meshParathyroid Hormone-Related Protein-
dc.subject.meshPhosphopyruvate Hydratase-
dc.subject.meshProstate-Specific Antigen-
dc.subject.meshProstatic Neoplasms-
dc.subject.meshProtein Tyrosine Phosphatases-
dc.subject.meshReceptor-Like Protein Tyrosine Phosphatases, Class 4-
dc.subject.meshReceptors, Androgen-
dc.subject.meshReceptors, Cell Surface-
dc.subject.meshTumor Cells, Cultured-
dc.titleAndrogen deprivation induces human prostate epithelial neuroendocrine differentiation of androgen-sensitive LNCaP cells.en
dc.typeArticleen
dc.identifier.journalEndocrine-related canceren

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