Gene profiling and pathway analysis of neuroendocrine transdifferentiated prostate cancer cells.
BACKGROUND
Neuroendocrine (NE) cells are present in both normal prostate and prostate cancer. In addition, NE differentiation can be induced by various factors, such as IL-6, in vitro and in vivo. However, the mechanism of this differentiation and the role of NE cells in prostate cancer are not well understood. In this study, we evaluated the gene expression and analyzed the pathways in prostate cancer cells exposed to various NE differentiation inducing factors in vitro.


METHODS
Gene expression signatures between control LNCaP cells and each treatment induced NE cell line were compared using Affymetrix GeneChip with network and pathway analysis.


RESULTS
All treatments were able to transdifferentiate LNCaP cells into NE phenotype as shown by morphology changes and NE marker measurements. Of the 54,675 oligonucleotide-based probe sets in microarray, 44,975 were mapped into the Ingenuity Pathway Analysis database and were filtered according to the t-test P value. At P < 0.002, the number of genes that were differentially expressed included 302 of the IL-6 treated cells, 201 of genistein, 233 of epinephrine, and 191 of the charcoal stripped serum ones. A pooled data approach also showed 346 differentially expressed genes at the same P value. Gene ontology analysis showed that cancer-related function had the highest significance.


CONCLUSIONS
Despite some overlap, each NE transdifferentiation inducing treatment was associated with a changed expression of a unique set of genes, and such gene profiling may help to elucidate the molecular mechanisms involved in NE transdifferentiation of prostate cancer cells.
Mori
Ryutaro
R
Department of Medicine, Division of Medical Oncology, University of Southern California Keck School of Medicine, Los Angeles, California, USA.
Xiong
Shigang
S
Wang
Qingcai
Q
Tarabolous
Chad
C
Shimada
Hiroshi
H
Panteris
Eleftherios
E
Danenberg
Kathleen D
KD
Danenberg
Peter V
PV
Pinski
Jacek K
JK
D016588:Anticarcinogenic Agents / Q000494:pharmacology; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D030541:Databases, Genetic; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D008297:Male; D009490:Neurosecretory Systems / Q000166:cytology*; D020411:Oligonucleotide Array Sequence Analysis; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016588:Anticarcinogenic Agents; D015850:Interleukin-6; D019833:Genistein; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human