Expression and mutational analysis of the MADR2/Smad2 gene in human prostate cancer.
BACKGROUND
Loss of heterozygosity (LOH) on chromosome arm 18q is common in sporadic prostate cancer and may be involved in cancer development through inactivation of tumor-suppressor genes (TSG). Recent identification, at 18q21.1, of MADR2/Smad2, a key component in transforming growth factor beta (TGFbeta)-family signaling pathways, led us to investigate the role of this gene in prostate tumorigenesis.


METHODS
Sporadic primary prostate tumors from 25 patients with clinically localized tumors and 7 with metastatic forms were examined for MADR2/Smad2 mutations by using polymerase chain reaction-single-strand conformational polymorphism (PCR-SSCP) analysis of cDNA, and for gene expression by quantitative reverse transcription-polymerase chain reaction (RT-PCR).


RESULTS
We detected no mutation in MADR2/Smad2 and no abnormal mRNA expression.


CONCLUSIONS
Despite recent evidence indicating that MADR2/Smad2 acts as a tumor-suppressor gene, our findings suggest a limited role of this gene in prostate tumorigenesis, at least in the early stages. Another key tumor-suppressor gene may therefore be the main target of the observed LOH at 18q21.1.
Laboratoire d'Oncogénétique, Centre René Huguenin, St.-Cloud, France.
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Latil
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Valéri
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Fournier
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Cussenot
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Lidereau
D001707:Biopsy, Needle; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D018076:DNA, Complementary / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics*; D004587:Electrophoresis, Agar Gel; D004591:Electrophoresis, Polyacrylamide Gel; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor / Q000235:genetics; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics*; D008297:Male; D018807:Polymorphism, Single-Stranded Conformational; D011467:Prostate / Q000737:chemistry / Q000503:physiopathology*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000737:chemistry / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D051899:Smad2 Protein; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000737:chemistry / Q000235:genetics
D017931:DNA Primers; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C497782:SMAD2 protein, human; D051899:Smad2 Protein; D015534:Trans-Activators; D016212:Transforming Growth Factor beta