Expression profiling of a human cell line model of prostatic cancer reveals a direct involvement of interferon signaling in prostate tumor progression.
Cancer-associated fibroblasts induce malignant behavior in genetically initiated but nontumorigenic human prostatic epithelium. The genetic basis for such transformation is still unknown. By using Affymetrix GeneChip technology, we profiled genomewide gene expression of transformed [tumorigenic benign prostatic hyperplasia (BPH1)(CAFTD)] and parental (nontumorigenic BPH1) cells. We identified differentially expressed genes, which are associated with tumorigenesis or tumor progression. One striking finding is that a significant portion of the down-regulated genes belongs to interferon (IFN)-inducible molecules. We show that IFN inhibited the tumorigenic BPH1(CAFTD) cell proliferation and colony formation in vitro and inhibited tumor growth in xenografts in vivo. Expression of the IFN-inducible molecules correlates with the growth-inhibiting effects of IFN. In addition, these genes are reported to be mapped mainly to two chromosomal regions, 10q23-26 and 17q21, which are frequently deleted in human prostate cancers. Furthermore, in silico data-mining with the GeneLogic database revealed that expression of the IFN-inducible genes was down-regulated in approximately 30% of the 49 clinically characterized samples of prostatic adenocarcinomas. Collectively, we show that there seems to be a direct link between IFN-inducible molecules and prostatic tumor progression. These findings suggest IFN-inducible molecules as potential therapeutic targets for the treatment of prostate cancer.
Shou
Jianyong
J
Department of Molecular Oncology, MS No. 72, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Soriano
Robert
R
Hayward
Simon W
SW
Cunha
Gerald R
GR
Williams
P Mickey
PM
Gao
Wei-Qiang
WQ
D002455:Cell Division / Q000187:drug effects; D018450:Disease Progression; D015536:Down-Regulation; D015870:Gene Expression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011470:Prostatic Hyperplasia; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D016898:Interferon-alpha; D007371:Interferon-gamma; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)