Differential expression of osteocalcin during the metastatic progression of prostate cancer

Thomas Gardner, Sang Jin Lee, Sang Don Lee, Xiong Li, Toshihiro Shirakawa, Dong Deuk Kwon, Ra Young Park, Kyu Youn Ahn, Chaeyong Jung

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Osteocalcin expression is restricted to osteoblasts and serum osteocalcin level is elevated in metastatic bone tumors including prostate tumors, which predominantly metastasizes to the bone and causes typical osteoblastic lesions. Previously, we have reported that osteocalcin RNA is widely expressed but incompletely spliced in the prostate including prostate tumors. Considering that many studies using osteocalcin-driven gene therapy have been conducted to treat hormone refractory metastatic tumors, detailed mechanisms controlling osteocalcin expression needs to be clarified. We aim to learn how osteocalcin expression is regulated during the metastatic process of prostate cancer. We applied assays of immunohistochemistry and RNA in situ hybridization in prostate tumors acquired from prostate (15) and metastatic sites, 13 from lymph node and 14 from bone. RT-PCR analysis in various cultured prostate cells was also performed. As predicted, osteocalcin RNA was highly expressed in most prostate epithelial cells of tumors, regardless of metastatic status of the tumor. However, osteocalcin protein was undetectable in tumors acquired from the primary site or lymph nodes whereas protein was highly expressed in the majority of bone-metastasized prostate tumors. RT-PCR analysis demonstrated that there was more completely spliced form of osteocalcin RNA present in bone-derived prostate cancer cells. Our data suggest that osteocalcin RNA was expressed but not completely spliced in non-bone environment, ultimately resulting in improper production of osteocalcin protein. This study explains why serum osteocalcin level is increased in patients with bone-metastasized prostate cancers. Yet, it remains to be clarified what regulates bone-specific osteocalcin RNA splicing in prostate tumors.

Original languageEnglish
Pages (from-to)903-908
Number of pages6
JournalOncology Reports
Volume21
Issue number4
DOIs
StatePublished - 2009

Fingerprint

Osteocalcin
Prostatic Neoplasms
Prostate
Bone and Bones
Neoplasms
RNA
Lymph Nodes
RNA Splicing
Polymerase Chain Reaction
Proteins
Serum
Osteoblasts
Genetic Therapy
In Situ Hybridization
Cultured Cells
Epithelial Cells
Immunohistochemistry

Keywords

  • Metastasis
  • Osteocalcin
  • Prostate cancer

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Gardner, T., Lee, S. J., Lee, S. D., Li, X., Shirakawa, T., Kwon, D. D., ... Jung, C. (2009). Differential expression of osteocalcin during the metastatic progression of prostate cancer. Oncology Reports, 21(4), 903-908. https://doi.org/10.3892/or_00000302

Differential expression of osteocalcin during the metastatic progression of prostate cancer. / Gardner, Thomas; Lee, Sang Jin; Lee, Sang Don; Li, Xiong; Shirakawa, Toshihiro; Kwon, Dong Deuk; Park, Ra Young; Ahn, Kyu Youn; Jung, Chaeyong.

In: Oncology Reports, Vol. 21, No. 4, 2009, p. 903-908.

Research output: Contribution to journalArticle

Gardner, T, Lee, SJ, Lee, SD, Li, X, Shirakawa, T, Kwon, DD, Park, RY, Ahn, KY & Jung, C 2009, 'Differential expression of osteocalcin during the metastatic progression of prostate cancer', Oncology Reports, vol. 21, no. 4, pp. 903-908. https://doi.org/10.3892/or_00000302
Gardner, Thomas ; Lee, Sang Jin ; Lee, Sang Don ; Li, Xiong ; Shirakawa, Toshihiro ; Kwon, Dong Deuk ; Park, Ra Young ; Ahn, Kyu Youn ; Jung, Chaeyong. / Differential expression of osteocalcin during the metastatic progression of prostate cancer. In: Oncology Reports. 2009 ; Vol. 21, No. 4. pp. 903-908.
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