Early growth response-1 gene: potential radiation response gene marker in prostate cancer.
This study was undertaken to determine whether the transcription factor EGR-1 expression: (1) in the primary tumor, correlates with radiation response in terms of complete local tumor control with no evidence of disease or recurrence and no evidence of metastasis; (2) in the postirradiated biopsies correlates with residual tumor; and (3) correlates with the expression of Egr-1 target genes such as TP53, pRB, and Bax. The authors analyzed: (1) 25 pretreated surgically resected paraffin-embedded primary adenocarcinomas of the prostate for the presence of EGR-1 expression and mutation, and correlated this with clinical endpoints such as serum prostate-specific antigen levels and current clinical status; (2) 27 postirradiated biopsies of prostate for the presence of EGR-1 expression, and correlated these findings to the residual tumor status; and (3) 12 prospective prostate tumor specimens for EGR-1 expression and its target genes. EGR-1 expression was determined by immunohistochemistry and mutations were screened in two regions of the Egr-1 gene (trinucleotide AGC repeats in transactivation domain [TD] and poly A tract in 3'UTR) by polymerase chain reaction-single strand conformational polymorphism analysis. Of 25 patients, 18 patients showed expression of EGR-1. EGR-1 overexpression correlated with treatment failure. No correlation with EGR-1 overexpression and its target genes was found, which may indirectly suggest that overexpressed EGR-1 may lack transactivation function. In summary, EGR-1 overexpression in the mutant form may provide an indication of clinical failure (local recurrence or metastasis).
Ahmed
M M
MM
Department of Radiation Medicine, University of Kentucky, Lexington, 40536-0084, USA.
Chendil
D
D
Lele
S
S
Venkatasubbarao
K
K
Dey
S
S
Ritter
M
M
Rowland
R G
RG
Mohiuddin
M
M
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D051766:Early Growth Response Protein 1; D006801:Humans; D017874:Immediate-Early Proteins; D007150:Immunohistochemistry; D008297:Male; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D017211:Treatment Failure
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D017874:Immediate-Early Proteins; D014157:Transcription Factors