Antisense-MDM2 Sensitizes LNCaP Prostate Cancer Cells to Androgen Deprivation, Radiation, and the Combination In Vivo

International Journal of Radiation Oncology Biology Physics

Volumn 68, Issue 4, 2007, Pages 1151-1160

  Stoyanova, Radka ^a   Hachem, Paul ^a   Hensley, Harvey ^a   Khor, Li Yan ^a   Mu, Zhaomei ^a   Hammond, M Elizabeth H ^b   Agrawal, Sudhir ^c   Pollack, Alan ^a  

^a FOX CHASE CANCER CENTER   (United States)

^b LDS HOSPITAL   (United States)

^c HYBRIDON INC   (United States)

Author keywords

Antisense MDM2; In vivo tumor model; MRI; Prostate cancer; Radiation

Indexed keywords

ANDROGEN DEPRIVATION (AD); ORTHOTOPIC MODELS; PROSTATE CANCER; PROSTATE SPECIFIC ANTIGEN (PSA);

CELLS; HISTOLOGY; IMMUNOLOGY; MAGNETIC RESONANCE IMAGING; TUMORS;

GENETIC ENGINEERING;

ANDROGEN; FORMALDEHYDE; KI 67 ANTIGEN; PROSTATE SPECIFIC ANTIGEN; PROTEIN MDM2; PROTEIN P21; PROTEIN P53;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CANCER CELL; CELL GROWTH; CELL STRAIN LNCAP; CHEMICAL ANALYSIS; DRUG EFFECT; DRUG INHIBITION; DRUG SENSITIZATION; GROWTH CURVE; IMAGE ANALYSIS; IMMUNOHISTOCHEMISTRY; IN VIVO STUDY; MALE; MICROMETASTASIS; MOUSE; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; NUDE MOUSE; PRIORITY JOURNAL; PROSTATE; PROSTATE CANCER; PROTEIN EXPRESSION; RADIATION; STAINING; STATISTICAL SIGNIFICANCE; TREATMENT FAILURE; TUMOR GROWTH; TUMOR VOLUME; WILD TYPE;

ANIMALS; CELL LINE, TUMOR; COMBINED MODALITY THERAPY; MAGNETIC RESONANCE IMAGING; MALE; MICE; MICE, NUDE; OLIGONUCLEOTIDES, ANTISENSE; ORCHIECTOMY; PROSTATE-SPECIFIC ANTIGEN; PROSTATIC NEOPLASMS; PROTO-ONCOGENE PROTEINS C-MDM2; RADIATION TOLERANCE; RADIOTHERAPY DOSAGE; TRANSPLANTATION, HETEROLOGOUS; TUMOR BURDEN;

EID: 34447304367     PISSN: 03603016     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ijrobp.2007.03.047     Document Type: Article

References (52)

1. Osman I., Drobnjak M., Fazzari M., et al. Inactivation of the p53 pathway in prostate cancer: Impact on tumor progression. Clin Cancer Res 5 (1999) 2082-2088
2. Leite K., Franco M., Strougi M., et al. Abnormal expression of MDM2 in prostate carcinoma. Mod Pathol 14 (2001) 428-436
3. Khor L.Y., Desilvio M., Al-Saleem T., et al. MDM2 as a predictor of prostate carcinoma outcome: An analysis of Radiation Therapy Oncology Group Protocol 8610. Cancer 104 (2005) 962-967
4. Haupt Y., Maya R., Kazaz A., and Oren M. Mdm2 promotes the rapid degradation of p53. Nature 387 (1997) 296-299
5. Honda R., Tanaka H., and Yasuda H. Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53. FEBS Lett 420 (1997) 25-27
6. Kubbutat M.H., Jones S.N., and Vousden K.H. Regulation of p53 stability by Mdm2. Nature 387 (1997) 299-303
7. Tao W., and Levine A.J. Nucleocytoplasmic shuttling of oncoprotein Hdm2 is required for Hdm2-mediated degradation of p53. Proc Natl Acad Sci U S A 96 (1999) 3077-3080
8. Zhang Z., Wang H., Li M., et al. MDM2 is a negative regulator of p21WAF1/CIP1, independent of p53. J Biol Chem 279 (2004) 16000-16006
9. Shieh S.Y., Ikeda M., Taya Y., et al. DNA damage-induced phosphorylation of p53 alleviates inhibition by MDM2. Cell 91 (1997) 325-334
10. Maki C.G. Oligomerization is required for p53 to be efficiently ubiquitinated by MDM2. J Biol Chem 274 (1999) 16531-16535
11. Chehab N.H., Malikzay A., Stavridi E.S., et al. Phosphorylation of Ser-20 mediates stabilization of human p53 in response to DNA damage. Proc Natl Acad Sci U S A 96 (1999) 13777-13782
12. Maya R., Balass M., Kim S.T., et al. ATM-dependent phosphorylation of Mdm2 on serine 395: Role in p53 activation by DNA damage. Genes Dev 15 (2001) 1067-1077
13. Lin H.K., Wang L., Hu Y.C., et al. Phosphorylation-dependent ubiquitylation and degradation of androgen receptor by Akt require Mdm2 E3 ligase. EMBO J 21 (2002) 4037-4048
14. Gaughan L., Logan I.R., Neal D.E., et al. Regulation of androgen receptor and histone deacetylase 1 by Mdm2-mediated ubiquitylation. Nucleic Acids Res 33 (2005) 13-26
15. Zhang Z., Wang H., Li M., et al. Stabilization of E2F1 protein by MDM2 through the E2F1 ubiquitination pathway. Oncogene 24 (2005) 7238-7247
16. Berges R., Vukanovic J., Epstein J., et al. Implication of cell kinetic changes during progression of human prostatic cancer. Clin Cancer Res 1 (1995) 473-480
17. Colombel M., Symmans F., Gil S., et al. Detection of the apoptosis-suppressing oncoprotein bcl-2 in hormone-refractory human prostate cancers. Am J Pathol 143 (1993) 390-400
18. McDonnell T.J., Navone N.M., Troncoso P., et al. Expression of bcl-2 oncoprotein and p53 protein accumulation in bone marrow metastases of androgen independent prostate cancer. J Urol 157 (1997) 569-574
19. Apakama I., Robinson M.C., Walter N.M., et al. bcl-2 overexpression combined with p53 protein accumulation correlates with hormone-refractory prostate cancer. Br J Cancer 74 (1996) 1258-1262
20. Burchardt M., Burchardt T., Shabsigh A., et al. Reduction of wild type p53 function confers a hormone resistant phenotype on LNCaP prostate cancer cells. Prostate 48 (2001) 225-230
21. Grunbaum U., Meye A., Bache M., et al. Transfection with mdm2-antisense or wtp53 results in radiosensitization and an increased apoptosis of a soft tissue sarcoma cell line. Anticancer Res 21 (2001) 2065-2071
22. Agrawal S., Kandimalla E.R., Yu D., et al. Potentiation of antitumor activity of irinotecan by chemically modified oligonucleotides. Int J Oncol 18 (2001) 1061-1069
23. Wang H., Nan L., Yu D., et al. Anti-tumor efficacy of a novel antisense anti-MDM2 mixed-backbone oligonucleotide in human colon cancer models: p53-dependent and p53-independent mechanisms. Mol Med 8 (2002) 185-199
24. Wang H., Yu D., Agrawal S., et al. Experimental therapy of human prostate cancer by inhibiting MDM2 expression with novel mixed-backbone antisense oligonucleotides: In vitro and activities and mechanisms. Prostate 54 (2003) 194-205
25. Zhang Z., Li M., Wang H., et al. Antisense therapy targeting MDM2 oncogene in prostate cancer: Effects on proliferation, apoptosis, multiple gene expression, and chemotherapy. Proc Natl Acad Sci U S A 100 (2003) 11636-11641
26. Zhang Z., Wang H., Prasad G., et al. Radiosensitization by antisense anti-MDM2 mixed-backbone oligonucleotide in in vitro and in vivo human cancer models. Clin Cancer Res 10 (2004) 1263-1273
27. Mu Z., Hachem P., Agrawal S., et al. Antisense MDM2 oligonucleotides restore the apoptotic response of prostate cancer cells to androgen deprivation. Prostate 60 (2004) 187-196
28. Edlund M., Sung S.Y., and Chung L.W. Modulation of prostate cancer growth in bone microenvironments. J Cell Biochem 91 (2004) 686-705
29. Sung S.Y., and Chung L.W. Prostate tumor-stroma interaction: Molecular mechanisms and opportunities for therapeutic targeting. Differentiation 70 (2002) 506-521
30. Zhang R., Lu Z., Zhao H., et al. In vivo stability, disposition and metabolism of a "hybrid" oligonucleotide phosphorothioate in rats. Biochem Pharmacol 50 (1995) 545-556
31. Agrawal S., Jiang Z., Zhao Q., et al. Mixed-backbone oligonucleotides as second generation antisense oligonucleotides: In vitro and in vivo studies. Proc Natl Acad Sci U S A 94 (1997) 2620-2625
32. Pollack A., Salem N., Ashoori F., et al. Lack of prostate cancer radiosensitization by androgen deprivation. Int J Radiat Oncol Biol Phys 51 (2001) 1002-1007
33. Cowen D., Salem N., Ashoori F., et al. Prostate cancer radiosensitization in vivo with adenovirus-mediated p53 gene therapy. Clin Cancer Res 6 (2000) 4402-4408
34. Mu Z., Hachem P., Agrawal S., et al. Antisense MDM2 sensitizes prostate cancer cells to androgen deprivation, radiation, and the combination. Int J Radiat Oncol Biol Phys 58 (2004) 336-343
35. Khor L.Y., DeSilvio M., McDonnell T.J., et al. Bcl-2 and bax expression and prostate cancer outcome in men treated with radiotherapy in Radiation Therapy Oncology Group protocol 86-10. Cancer 66 (2006) 25-30
36. Young C.Y., Andrews P.E., Montgomery B.T., et al. Tissue-specific and hormonal regulation of human prostate-specific glandular kallikrein. Biochemistry 31 (1992) 818-824
37. Zhang S., Murtha P.E., and Young C.Y. Defining a functional androgen responsive element in the 5′ far upstream flanking region of the prostate-specific antigen gene. Biochem Biophys Res Commun 231 (1997) 784-788
38. Thalmann G.N., Sikes R.A., Chang S.M., et al. Suramin-induced decrease in prostate-specific antigen expression with no effect on tumor growth in the LNCaP model of human prostate cancer. J Natl Cancer Inst 88 (1996) 794-801
39. Agus D.B., Golde D.W., Sgouros G., et al. Positron emission tomography of a human prostate cancer xenograft: Association of changes in deoxyglucose accumulation with other measures of outcome following androgen withdrawal. Cancer Res 58 (1998) 3009-3014
40. Endl E., Hollmann C., and Gerdes J. Antibodies against the Ki-67 protein: Assessment of the growth fraction and tools for cell cycle analysis. Methods Cell Biol 63 (2001) 399-418
41. Endl E., Kausch I., Baack M., et al. The expression of Ki-67, MCM3, and p27 defines distinct subsets of proliferating, resting, and differentiated cells. J Pathol 195 (2001) 457-462
42. Pollack A., Joon D.L., Wu C.S., et al. Quiescence in R3327-G rat prostate tumors after androgen ablation. Cancer Res 57 (1997) 2493-2500
43. Pilepich M.V., Winter K., John M.J., et al. Phase III radiation therapy oncology group (RTOG) trial 86-10 of androgen deprivation adjuvant to definitive radiotherapy in locally advanced carcinoma of the prostate. Int J Radiat Oncol Biol Phys 50 (2001) 1243-1252
44. Pilepich M.V., Winter K., Lawton C.A., et al. Androgen suppression adjuvant to definitive radiotherapy in prostate carcinoma-long-term results of phase III RTOG 85-31. Int J Radiat Oncol Biol Phys 61 (2005) 1285-1290
45. Bolla M., Collette L., Blank L., et al. Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): A phase III randomised trial. Lancet 360 (2002) 103-106
46. Denham J.W., Steigler A., Lamb D.S., et al. Short-term androgen deprivation and radiotherapy for locally advanced prostate cancer: Results from the Trans-Tasman Radiation Oncology Group 96.01 randomised controlled trial. Lancet Oncol 6 (2005) 841-850
47. Pollack A., Zagars G.K., Starkschall G., et al. Prostate cancer radiation dose response: Results of the M. D. Anderson phase III randomized trial. Int J Radiat Oncol Biol Phys 53 (2002) 1097-1105
48. Pollack A., Zagars G.K., Antolak J.A., et al. Prostate biopsy status and PSA nadir level as early surrogates for treatment failure: Analysis of a prostate cancer randomized radiation dose escalation trial. Int J Radiat Oncol Biol Phys 54 (2002) 677-685
49. Jacob R., Hanlon A.L., Horwitz E.M., et al. The relationship of increasing radiotherapy dose to reduced distant metastases and mortality in men with prostate cancer. Cancer 100 (2004) 538-543
50. Wang H., Oliver P., Zhang Z., et al. Chemosensitization and radiosensitization of human cancer by antisense anti-MDM2 oligonucleotides: In vitro and in vivo activities and mechanisms. Ann N Y Acad Sci 1002 (2003) 217-235
51. Zhang R., Wang H., and Agrawal S. Novel antisense anti-MDM2 mixed-backbone oligonucleotides: Proof of principle, in vitro and in vivo activities, and mechanisms. Curr Cancer Drug Targets 5 (2005) 43-49
52. Pollack A., DeSilvio M., Khor L.Y., et al. Ki-67 staining is a strong predictor of distant metastasis and mortality for men with prostate cancer treated with radiotherapy plus androgen deprivation: Radiation Therapy Oncology Group Trial 92-02. J Clin Oncol 22 (2004) 2133-2140