Early growth response-1 gene - Potential radiation response gene marker in prostate cancer

被引:17
作者
Ahmed, MM
Chendil, D
Lele, S
Venkatasubbarao, K
Dey, S
Ritter, M
Rowland, RG
Mohiuddin, M
机构
[1] Univ Kentucky, Dept Radiat Med, UKMC, Lexington, KY 40536 USA
[2] Univ Kentucky, Dept Pathol, Lexington, KY USA
[3] Univ Kentucky, Dept Surg, Div Urol, Lexington, KY USA
来源
AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS | 2001年 / 24卷 / 05期
关键词
prostate cancer; radiation; EGR-1; gene overexpression; radiation resistance; apoptosis;
D O I
10.1097/00000421-200110000-00017
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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).
引用
收藏
页码:500 / 505
页数:6
相关论文
共 40 条
  • [1] Ionizing radiation-inducible apoptosis in the absence of p53 linked to transcription factor EGR-1
    Ahmed, MM
    Sells, SF
    Venkatasubbarao, K
    Fruitwala, SM
    Muthukkumar, S
    Harp, C
    Mohiuddin, M
    Rangnekar, VM
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (52) : 33056 - 33061
  • [2] EGR-1 induction is required for maximal radiosensitivity in A375-C6 melanoma cells
    Ahmed, MM
    Venkatasubbarao, K
    Fruitwala, SM
    Muthukkumar, S
    Wood, DP
    Sells, SF
    Mohiuddin, M
    Rangnekar, VM
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (46) : 29231 - 29237
  • [3] Beahrs O H, 1984, Bull Am Coll Surg, V69, P16
  • [4] RADIATION-INJURY OF THE NORMAL AND NEOPLASTIC PROSTATE
    BOSTWICK, DG
    EGBERT, BM
    FAJARDO, LF
    [J]. AMERICAN JOURNAL OF SURGICAL PATHOLOGY, 1982, 6 (06) : 541 - 551
  • [5] BRUCE AW, 1979, CAN J SURG, V22, P424
  • [6] COX JD, 1977, CANCER, V40, P156, DOI 10.1002/1097-0142(197707)40:1<156::AID-CNCR2820400126>3.0.CO
  • [7] 2-#
  • [8] CLINICAL RELEVANCE OF TRANS-RECTAL ULTRASOUND, BIOPSY, AND SERUM PROSTATE-SPECIFIC ANTIGEN FOLLOWING EXTERNAL-BEAM RADIOTHERAPY FOR CARCINOMA OF THE PROSTATE
    CROOK, J
    ROBERTSON, S
    COLLIN, G
    ZALESKI, V
    ESCHE, B
    [J]. INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 1993, 27 (01): : 31 - 37
  • [9] DAS A, 2000, J BIOL CHEM, V16, P16
  • [10] DAS A, 2000, 91 ANN M AM ASS CANC, P546