Title of article :
Genome-wide expression profiling reveals transcriptomic variation and perturbed gene networks in androgen-dependent and androgen-independent prostate cancer cells
Author/Authors :
Singh، نويسنده , , Ajay P. and Bafna، نويسنده , , Sangeeta and Chaudhary، نويسنده , , Kunal and Venkatraman، نويسنده , , Ganesh and Smith، نويسنده , , Lynette and Eudy، نويسنده , , James D. and Johansson، نويسنده , , Sonny L. and Lin، نويسنده , , Ming-Fong and Batra، نويسنده , , Surinder K.، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2008
Pages :
11
From page :
28
To page :
38
Abstract :
Previously, we have developed a unique in vitro LNCaP cell model, which includes androgen-dependent (LNCaP-C33), androgen-independent (LNCaP-C81) and an intermediate phenotype (LNCaP-C51) cell lines resembling the stages of prostate cancer progression to hormone independence. This model is advantageous in overcoming the heterogeneity associated with the prostate cancer up to a certain extent. We characterized and compared the gene expression profiles in LNCaP-C33 (androgen-dependent) and LNCaP-C81 (androgen-independent) cells using Affymetrix GeneChip array analyses. Multiple genes were identified exhibiting differential expression during androgen-independent progression. Among the important genes upregulated in androgen-independent cells were PCDH7, TPTE, TSPY, EPHA3, HGF, MET, EGF, TEM8, etc., whereas many candidate tumor suppressor genes (HTATIP2, CDKN2A, CDKN2B, CDKN1C, TP53, TP73, ICAM1, SOCS1/2, SPRY2, PPP2CA, PPP3CA, etc.) were decreased. Pathway prediction analysis identified important gene networks associated with growth-promoting and apoptotic signaling that were perturbed during androgen-independent progression. Further investigation of one of the genes, PPP2CA, which encodes the catalytic subunit of a serine phosphatase PP2A, a potent tumor suppressor, revealed that its expression was decreased in prostate cancer compared to adjacent normal/benign tissue. Furthermore, the downregulated expression of PPP2CA was significantly correlated with tumor stage and Gleason grade. Future studies on the identified differentially expressed genes and signaling pathways may be helpful in understanding the biology of prostate cancer progression and prove useful in developing novel prognostic biomarkers and therapy for androgen-refractory prostate cancer.
Keywords :
prostate cancer , Gene expression , Transcriptomic variation , Androgen-independence , Gene networks
Journal title :
Cancer Letters
Serial Year :
2008
Journal title :
Cancer Letters
Record number :
1811212
Link To Document :
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