Deregulation of a Hox protein regulatory network spanning prostate cancer initiation and progression

James L. Chen, Jianrong Li, Kyle J. Kiriluk, Alex M. Rosen, Gladell P. Paner, Tatjana Antic, Yves A Lussier, Donald J. Vander Griend

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Purpose: The aberrant activity of developmental pathways in prostate cancer may provide significant insight into predicting tumor initiation and progression, as well as identifying novel therapeutic targets. To this end, despite shared androgen-dependence and functional similarities to the prostate gland, seminal vesicle cancer is exceptionally rare. Experimental Design: We conducted genomic pathway analyses comparing patient-matched normal prostate and seminal vesicle epithelial cells to identify novel pathways for tumor initiation and progression. Derived gene expression profiles were grouped into cancer biomodules using a protein-protein network algorithm to analyze their relationship to known oncogenes. Each resultant biomodule was assayed for its prognostic ability against publically available prostate cancer patient gene array datasets. Results: Analyses show that the embryonic developmental biomodule containing four homeobox gene family members (Meis1, Meis2, Pbx1, and HoxA9) detects a survival difference in a set of watchful-waiting patients (n = 172, P = 0.05), identify men who are more likely to recur biochemically postprostatectomy (n = 78, P = 0.02), correlate with Gleason score (r = 0.98, P = 0.02), and distinguish between normal prostate, primary tumor, and metastatic disease. In contrast to other cancer types, Meis1, Meis2, and Pbx1 expression is decreased in poor-prognosis tumors, implying that they function as tumor suppressor genes for prostate cancer. Immunohistochemical staining documents nuclear basal-epithelial and stromal Meis2 staining, with loss of Meis2 expression in prostate tumors. Conclusion: These data implicate deregulation of the Hox protein cofactors Meis1, Meis2, and Pbx1 as serving a critical function to suppress prostate cancer initiation and progression.

Original languageEnglish (US)
Pages (from-to)4291-4302
Number of pages12
JournalClinical Cancer Research
Volume18
Issue number16
DOIs
StatePublished - Aug 15 2012
Externally publishedYes

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Prostatic Neoplasms
Prostate
Neoplasms
Proteins
Seminal Vesicles
Watchful Waiting
Staining and Labeling
Aptitude
Neoplasm Grading
Homeobox Genes
Neoplasm Genes
Tumor Suppressor Genes
Oncogenes
Transcriptome
Androgens
Research Design
Epithelial Cells
Survival

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Chen, J. L., Li, J., Kiriluk, K. J., Rosen, A. M., Paner, G. P., Antic, T., ... Vander Griend, D. J. (2012). Deregulation of a Hox protein regulatory network spanning prostate cancer initiation and progression. Clinical Cancer Research, 18(16), 4291-4302. https://doi.org/10.1158/1078-0432.CCR-12-0373

Deregulation of a Hox protein regulatory network spanning prostate cancer initiation and progression. / Chen, James L.; Li, Jianrong; Kiriluk, Kyle J.; Rosen, Alex M.; Paner, Gladell P.; Antic, Tatjana; Lussier, Yves A; Vander Griend, Donald J.

In: Clinical Cancer Research, Vol. 18, No. 16, 15.08.2012, p. 4291-4302.

Research output: Contribution to journalArticle

Chen, JL, Li, J, Kiriluk, KJ, Rosen, AM, Paner, GP, Antic, T, Lussier, YA & Vander Griend, DJ 2012, 'Deregulation of a Hox protein regulatory network spanning prostate cancer initiation and progression', Clinical Cancer Research, vol. 18, no. 16, pp. 4291-4302. https://doi.org/10.1158/1078-0432.CCR-12-0373
Chen, James L. ; Li, Jianrong ; Kiriluk, Kyle J. ; Rosen, Alex M. ; Paner, Gladell P. ; Antic, Tatjana ; Lussier, Yves A ; Vander Griend, Donald J. / Deregulation of a Hox protein regulatory network spanning prostate cancer initiation and progression. In: Clinical Cancer Research. 2012 ; Vol. 18, No. 16. pp. 4291-4302.
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