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Inhibition of human chorionic gonadotropin beta-subunit modulates the mitogenic effect of c-myc in human prostate cancer cells.

Publication ,  Journal Article
Devi, GR; Oldenkamp, JR; London, CA; Iversen, PL
Published in: Prostate
November 1, 2002

BACKGROUND: Amplification of the proto-oncogene c-myc has been identified as one of the most common genetic alterations in prostate cancer, thus making it an attractive therapeutic target. However, certain prostate cancer cells are unresponsive to c-Myc inhibition. The purpose of this study was to test the hypothesis that effective growth inhibition in the refractory cancer cells can be achieved by blocking c-myc along with a growth factor using a novel phosphorodiamidate morpholino antisense oligomer-based approach. Human chorionic gonadotropin, a growth factor implicated in neoplasm, causes activation of c-myc through a G-protein-coupled pathway of signal transduction. METHODS: In this study, the effect of inhibition of beta-hCG and c-myc singly or in combination was evaluated in DU145 (RB -/-, p53-/-, androgen-independent) and LNCaP (Rb+/+, p53 +/+, androgen-sensitive) human prostate cancer cell lines and in a DU145 subcutaneous xenograft murine model. RESULTS: Antisense phosphorodiamidate morpholino oligomers directed against beta-hCG and c-myc caused a specific decrease of the target protein levels. Unlike LNCaP cells, DU145 cell growth was refractory to c-Myc inhibition. Unresponsiveness to c-myc inhibition in DU145 cells was overcome by targeting both beta-hCG and c-myc genes, resulting in potentiation of the antiproliferative effect seen with inhibition of beta-hCG alone. CONCLUSIONS: The inhibition of beta-hCG sensitizes prostate cancer cells to the antiproliferative effects of c-Myc inhibition, including tumors that are refractory to c-Myc decrease alone.

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Published In

Prostate

DOI

ISSN

0270-4137

Publication Date

November 1, 2002

Volume

53

Issue

3

Start / End Page

200 / 210

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Specific Pathogen-Free Organisms
  • Random Allocation
  • Proto-Oncogene Proteins c-myc
  • Proto-Oncogene Mas
  • Prostatic Neoplasms
  • Phosphorus Compounds
  • Oncology & Carcinogenesis
  • Oligonucleotides, Antisense
  • Morpholines
 

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Devi, G. R., Oldenkamp, J. R., London, C. A., & Iversen, P. L. (2002). Inhibition of human chorionic gonadotropin beta-subunit modulates the mitogenic effect of c-myc in human prostate cancer cells. Prostate, 53(3), 200–210. https://doi.org/10.1002/pros.10151
Devi, Gayathri R., Jennifer R. Oldenkamp, Carla A. London, and Patrick L. Iversen. “Inhibition of human chorionic gonadotropin beta-subunit modulates the mitogenic effect of c-myc in human prostate cancer cells.Prostate 53, no. 3 (November 1, 2002): 200–210. https://doi.org/10.1002/pros.10151.
Devi, Gayathri R., et al. “Inhibition of human chorionic gonadotropin beta-subunit modulates the mitogenic effect of c-myc in human prostate cancer cells.Prostate, vol. 53, no. 3, Nov. 2002, pp. 200–10. Pubmed, doi:10.1002/pros.10151.
Journal cover image

Published In

Prostate

DOI

ISSN

0270-4137

Publication Date

November 1, 2002

Volume

53

Issue

3

Start / End Page

200 / 210

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Specific Pathogen-Free Organisms
  • Random Allocation
  • Proto-Oncogene Proteins c-myc
  • Proto-Oncogene Mas
  • Prostatic Neoplasms
  • Phosphorus Compounds
  • Oncology & Carcinogenesis
  • Oligonucleotides, Antisense
  • Morpholines