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PMID: 16721365 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Increased expression of pAKT is associated with radiation resistance in cervical cancer.

British journal of cancer ·Vol. 94 ·No. 11 ·2006-06-05 ·Pages 1678-82

Kim TJ, Lee JW, Song SY, Choi JJ, Choi CH, Kim BG, Lee JH, Bae DS

Abstract

Phosphorylated AKT (pAKT) is a major contributor to radioresistance in human cancers. The aim of this study was to investigate the association of pAKT expression and radiation resistance in cervical cancer. A retrospective review was made of the records of 27 women who received primary radiation therapy due to locally advanced cervical cancer (LACC) with FIGO stage IIB-IVA. Nine patients regarded as radiation resistant developed local recurrences with a median progression free interval of 9 months. Eighteen patients did not show local recurrences, and were regarded as a radiation-sensitive group. Using pretreatment paraffin-embedded tissues, we evaluated pAKT expression by immunohistochemistry. A significant association was found between the level of pAKT expression and local recurrence. Immunohistochemical staining for pAKT was significantly more frequent in the radiation-resistant than in the radiation-sensitive group (P=0.004). The mean progression-free survival was 86 months for patients with pAKT-negative staining (19 cases) and 44 months for patients with pAKT-positive expression (eight cases) (P=0.008). These results suggest that signalling from phosphatidylinositide 3-kinase/pAKT can lead to radiation resistance, and that evaluation of pAKT may be a prognostic marker for response to radiotherapy in LACC.

MeSH Terms
Adult Aged Aged, 80 and over Disease Progression Female Gene Expression Regulation, Neoplastic/radiation effects Humans Immunohistochemistry Middle Aged Neoplasm Staging Oncogene Protein v-akt/genetics,metabolism Phosphorylation Radiation Tolerance/genetics Recurrence Uterine Cervical Neoplasms/genetics,pathology,radiotherapy
Chemicals
Oncogene Protein v-akt
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Kim T-J
Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Gangnam-gu, Seoul 135-710, Korea.
Lee J-W
Song S Y
Choi J-J
Choi C H
Kim B-G
Lee J-H
Bae D-S
References (33)
33 references, click to expand
  1. C225 antiepidermal growth factor receptor antibody enhances tumor radiocurability.
    Int J Radiat Oncol Biol Phys. 2001 Oct 1;51(2):474-7 PMID: 11567823
  2. Cervical epidermal growth factor-receptor (EGF-R) and serum insulin-like growth factor II (IGF-II) levels are potential markers for cervical cancer.
    Am J Reprod Immunol. 2000 Oct;44(4):222-30 PMID: 11076094
  3. Local recurrence in head and neck cancer: relationship to radiation resistance and signal transduction.
    Clin Cancer Res. 2002 Mar;8(3):885-92 PMID: 11895923
  4. Radiation sensitization of human cancer cells in vivo by inhibiting the activity of PI3K using LY294002.
    Int J Radiat Oncol Biol Phys. 2003 Jul 1;56(3):846-53 PMID: 12788194
  5. Phosphatidylinositide 3-kinase/AKT in radiation responses.
    Histol Histopathol. 2004 Jul;19(3):915-23 PMID: 15168354
  6. HER-2/neu blocks tumor necrosis factor-induced apoptosis via the Akt/NF-kappaB pathway.
    J Biol Chem. 2000 Mar 17;275(11):8027-31 PMID: 10713122
  7. Clinical and operative staging of cervical cancer.
    Baillieres Clin Obstet Gynaecol. 1988 Dec;2(4):747-59 PMID: 3067942
  8. The phosphatidylinositol 3-Kinase AKT pathway in human cancer.
    Nat Rev Cancer. 2002 Jul;2(7):489-501 PMID: 12094235
  9. Real-time ultrasonography for determination of ovarian morphology and volume. A possible early screening test for ovarian cancer?
    Lancet. 1982 Feb 20;1(8269):425-6 PMID: 6121093
  10. Increase of AKT/PKB expression correlates with gleason pattern in human prostate cancer.
    Int J Cancer. 2003 Nov 20;107(4):676-80 PMID: 14520710
  11. Activation of NF-kappaB and upregulation of intracellular anti-apoptotic proteins via the IGF-1/Akt signaling in human multiple myeloma cells: therapeutic implications.
    Oncogene. 2002 Aug 22;21(37):5673-83 PMID: 12173037
  12. AKT plays a central role in tumorigenesis.
    Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):10983-5 PMID: 11572954
  13. Immunohistochemical demonstration of phospho-Akt in high Gleason grade prostate cancer.
    Clin Cancer Res. 2002 Apr;8(4):1168-71 PMID: 11948129
  14. Correlation of cervical carcinoma c-erb B-2 oncogene with cell proliferation parameters in patients treated with radiation therapy for cervical carcinoma.
    Cancer. 1997 Feb 1;79(3):513-20 PMID: 9028362
  15. Oncogene alterations in carcinomas of the uterine cervix: overexpression of the epidermal growth factor receptor is associated with poor prognosis.
    Clin Cancer Res. 1999 Mar;5(3):577-86 PMID: 10100709
  16. Stress and radiation-induced activation of multiple intracellular signaling pathways.
    Radiat Res. 2003 Mar;159(3):283-300 PMID: 12600231
  17. Prognostic relevance of activated Akt kinase in node-negative breast cancer: a clinicopathological study of 99 cases.
    Mod Pathol. 2004 Jan;17(1):15-21 PMID: 14631376
  18. Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma.
    N Engl J Med. 1999 Apr 15;340(15):1154-61 PMID: 10202166
  19. Phosphatidylinositol 3-kinase inhibition by LY294002 radiosensitizes human cervical cancer cell lines.
    Clin Cancer Res. 2006 Jan 1;12(1):250-6 PMID: 16397049
  20. Analysis of the phosphatidylinositol 3'-kinase signaling pathway in glioblastoma patients in vivo.
    Cancer Res. 2003 Jun 1;63(11):2742-6 PMID: 12782577
  21. Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer.
    N Engl J Med. 1999 Apr 15;340(15):1137-43 PMID: 10202164
  22. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer.
    N Engl J Med. 1999 Apr 15;340(15):1144-53 PMID: 10202165
  23. Radical radiotherapy for locally advanced cancer of uterine cervix.
    Cancer Res Treat. 2004 Aug;36(4):222-7 PMID: 20368838
  24. PIK3CA as an oncogene in cervical cancer.
    Oncogene. 2000 May 25;19(23):2739-44 PMID: 10851074
  25. Tumour-proliferative fraction and growth factor expression as markers of tumour response to radiotherapy in cancer of the uterine cervix.
    J Cancer Res Clin Oncol. 1998;124(8):456-61 PMID: 9750023
  26. Cervical cancer.
    Lancet. 2003 Jun 28;361(9376):2217-25 PMID: 12842378
  27. Increased expression of ICAM-3 is associated with radiation resistance in cervical cancer.
    Int J Cancer. 2005 Nov 1;117(2):194-201 PMID: 15880373
  28. Antioxidant and redox regulation of gene transcription.
    FASEB J. 1996 May;10(7):709-20 PMID: 8635688
  29. Roles of mitogen-activated protein kinase and phosphoinositide 3'-kinase in ErbB2/ErbB3 coreceptor-mediated heregulin signaling.
    Exp Cell Res. 2003 Apr 1;284(2):291-302 PMID: 12651161
  30. Expression and prognostic significance of kit, protein kinase B, and mitogen-activated protein kinase in patients with small cell lung cancer.
    Clin Cancer Res. 2003 Jun;9(6):2241-7 PMID: 12796392
  31. Correlation between human epidermal growth factor receptor family (EGFR, HER2, HER3, HER4), phosphorylated Akt (P-Akt), and clinical outcomes after radiation therapy in carcinoma of the cervix.
    Gynecol Oncol. 2005 Nov;99(2):415-21 PMID: 16157365
  32. An essential role for free radicals and derived species in signal transduction.
    FASEB J. 1997 Feb;11(2):118-24 PMID: 9039953
  33. Long-term results of high-dose rate intracavitary brachytherapy for squamous cell carcinoma of the uterine cervix.
    Cancer. 2005 Jan 1;103(1):92-101 PMID: 15540233
Article Info
Journal
British journal of cancer
Abbr.
Br J Cancer
ISSN
0007-0920
Published
2006-06-05
Pages
1678-82
Language
English
Region
England
NLM ID
0370635
PMCID
PMC2361323
Subset
IM
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