Tumor progression is accompanied by significant changes in the levels of expression of polyamine metabolism regulatory genes and clusterin (sulfated glycoprotein 2) in human prostate cancer specimens.
Using Northern blotting, the expression levels of the genes for polyamine metabolism regulatory proteins and clusterin have been measured in a series of 23 human prostate cancers (CaPs) dissected from radical prostatectomy specimens. Patient matched, nontumor tissue was dissected from benign areas of the gland. The results indicate that transcripts encoding ornithine decarboxylase (ODC), ODC antizyme, adenosylmethionine decarboxylase, and spermidine/spermine N1-acetyltransferase (SSAT) were significantly higher, whereas clusterin (sulfated glycoprotein 2) mRNA was significantly lower in tumors compared with the benign tissue. All mRNA levels were compared with those of histone H3 and growth arrest-specific gene 1, markers of cell proliferation and cell quiescence, respectively, and glyceraldehyde 3-phosphate dehydrogenase, a housekeeping gene. In poorly differentiated and locally invasive CaPs and in tumors with unfavorable prognosis or total prostate-specific antigen (PSA) levels > 10.0 ng/ml at diagnosis, an overall increase in the levels of H3 mRNA and a decrease in growth arrest-specific gene 1 mRNA was detected, indicative of higher proliferation activity, whereas the differences in expression levels for the polyamine metabolism and clusterin genes were higher. ODC and SSAT changes were positively correlated in normal tissue but not in high-grade cancer, whereas ODC antizyme and SSAT changes were positively correlated in more malignant CaPs but not in normal tissue. Tumor classification based on the changes in expression levels of all of the genes studied could be correlated to differentiation grade and local invasiveness classification systems in 72.2 and 83.3% of the cases, respectively. In a 1-year follow-up period, three patients whose CaPs ranked as less aggressive according to clinical staging, but classified as advanced cancers with the proposed molecular classification, showed increases in total PSA levels, indicative of tumor relapse. Thus, molecular classification, based on gene expression, may enhance the available prognostic tools for prostate tumors.
Bettuzzi
S
S
Department of Scienze Biomediche, Università di Modena e Reggio Emilia, Modena, Italy.
Davalli
P
P
Astancolle
S
S
Carani
C
C
Madeo
B
B
Tampieri
A
A
Corti
A
A
Saverio
B
B
Pierpaola
D
D
Serenella
A
A
Cesare
C
C
Bruno
M
M
Auro
T
T
Arnaldo
C
C
D000123:Acetyltransferases / Q000378:metabolism; D012437:Adenosylmethionine Decarboxylase / Q000378:metabolism; D018797:Cell Cycle Proteins; D002455:Cell Division; D051152:Clusterin; D018450:Disease Progression; D058851:GPI-Linked Proteins; D015972:Gene Expression Regulation, Neoplastic; D005809:Genes, Regulator / Q000502:physiology*; D006023:Glycoproteins / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000378:metabolism*; D009955:Ornithine Decarboxylase / Q000378:metabolism; D011073:Polyamines / Q000378:metabolism*; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D011506:Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D000099228:Diamine N-Acetyltransferase
D000123:Acetyltransferases; D012437:Adenosylmethionine Decarboxylase; D018797:Cell Cycle Proteins; D051152:Clusterin; D058851:GPI-Linked Proteins; D006023:Glycoproteins; D006657:Histones; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D009955:Ornithine Decarboxylase; D011073:Polyamines; D011506:Proteins; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D000099228:Diamine N-Acetyltransferase; C495242:CLU protein, human; C066709:GAS1 protein, S cerevisiae; C096192:GAS1 protein, human; C031017:ornithine decarboxylase antizyme