Identification of differentially expressed genes in organ-confined prostate cancer by gene expression array.
BACKGROUND
To understand the molecular mechanisms underlying prostate cancer, we have utilized the gene expression array to search for genes whose expression is altered in this disease.


METHODS
RNA quality from manual microdissected tissue was compared with that from microselected tissue by electrophoresis. For array analysis, malignant and normal prostate epithelium was enriched using microselection technique from prostate cancer and the peripheral zone of a normal prostate. Identical array membrane was hybridized to labeled cancer and normal cDNA, respectively. The differentially expressed gene was further evaluated by RT-PCR.


RESULTS
Microdissection, but not microselection, causes visible degradation to RNA. Of the 588 genes on the membrane, 87 genes yielded significant signals. Based on a three fold difference relative to normal prostate tissue, 1 gene was overexpressed and 12 genes underexpressed in prostate cancer. Of them, five showed statistically significant reduction in mRNA levels in six prostate cancer specimens compared with seven normal prostate specimens. These five genes are glutathione S-transferase M1 (GSTM1), monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-alpha receptor-1 (TNFR-1), transforming growth factor beta3 (TGF-beta3), and inhibitor of DNA binding-1 (ID-1).


CONCLUSIONS
GST-based metabolism, cytokine MCP-1 and TNFR-1, and TGF-beta3 signaling pathways, and some helix-loop-helix nuclear proteins could be potentially important in organ-confined prostate cancer and deserve further investigation.
Chetcuti
A
A
Department of Medicine, University of Sydney, Sydney, NSW, Australia.
Margan
S
S
Mann
S
S
Russell
P
P
Handelsman
D
D
Rogers
J
J
Dong
Q
Q
D000328:Adult; D000368:Aged; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D004587:Electrophoresis, Agar Gel; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005982:Glutathione Transferase / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011467:Prostate / Q000378:metabolism / Q000502:physiology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D012334:RNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis / Q000235:genetics; D012097:Repressor Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics
D018932:Chemokine CCL2; D004268:DNA-Binding Proteins; C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1; D012334:RNA, Neoplasm; D018124:Receptors, Tumor Necrosis Factor; D012097:Repressor Proteins; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D005982:Glutathione Transferase