Gene expression in the LNCaP human prostate cancer progression model: progression associated expression in vitro corresponds to expression changes associated with prostate cancer progression in vivo.
Identification of the genes involved in prostate cancer (PCa) progression to a virulent and androgen-independent (AI) form is a major focus in the field. cDNA microarray was used to compare the gene expression profile of the indolent, androgen sensitive (AS) LNCaP PCa cell line to the aggressively metastatic, AI C4-2. Thirty-eight unique sequences from a 6388 cDNA array were found differentially expressed (> or =2-fold, 95% CI). The expression of 14 genes was lower in C4-2 than in LNCaP cells, while the reverse was true for 24 genes. Twelve genes were validated using Q-PCR, Western blotting and immunohistochemistry (IHC) of LNCaP and C4-2 xenograft. Q-PCR showed that 10 of 12 (83.3%) genes had similar patterns of expression to the array (LNCaP>C4-2: TMEFF2, ATP1B1, IL-8, BTG1, BChE, NKX3.1; LNCaP<C4-2: BNIP3, TM4SF1, AMACR, UCH-L1). By Western blot, 4/5 genes examined: TMEFF2, NKX3.1, AMACR, and UCH-L1, not IL-8, were consistent with RNA profiling. Protein expression levels were confirmed in human tumor xenografts using IHC. A large proportion of the markers found in this expression profile is consistent with those recently identified in human PCa tissues along with several novel genes that remain to be examined. These data further demonstrate the utility of the LNCaP human PCa progression model as a tool to investigate the phenotypic changes required for the progression to AI and metastasis.
Chen
Qian
Q
Laboratory for Cancer Ontogeny and Therapeutics, Department of Biological Sciences, University of Delaware, Wolf Hall, Newark, DE 19716, USA.
Watson
Jeffery T
JT
Marengo
Susan Ruth
SR
Decker
Keith S
KS
Coleman
Ilsa
I
Nelson
Peter S
PS
Sikes
Robert A
RA
D015153:Blotting, Western; D018450:Disease Progression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008954:Models, Biological; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D012334:RNA, Neoplasm