Tumor-suppression function of transcription factor USF2 in prostate carcinogenesis

N. Chen, M. N. Szentirmay, S. A. Pawar, M. Sirito, J. Wang, Z. Wang, Q. Zhai, H. X. Yang, D. M. Peehl, J. L. Ware, M. Sawadogo

Research output: Contribution to journalArticle

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Abstract

Although the transcription factor USF2 has been implicated in the regulation of cellular growth and proliferation, it is unknown whether alterations in USF2 contribute to tumorigenesis and tumor development. We examined the role of USF2 in prostate tumorigenesis. Western blot analysis revealed markedly decreased USF2 levels in three androgen-independent prostate cancer cell lines, PC-3, DU145, and M12, as compared to nontumorigenic prostate epithelial cells or the androgen-dependent cell line, LNCaP. Ectopic expression of USF2 in PC-3 cells did not affect the cell proliferation rate of PC-3 cells on plastic surfaces. However, it dramatically decreased anchorage-independent growth of PC-3 cells in soft agar (90-98% inhibition) and the invasion capability (80% inhibition) of PC-3 cells in matrix gel assay. Importantly, expression of USF2 in PC-3 cells inhibited the tumorigenicity of PC-3 cells in an in vivo nude mice xenograft model (80-90% inhibition). These results suggest that USF2 has tumor-suppression function. Consistent with its function in tumor suppression, we found that the USF2 protein is present in normal prostate epithelial cells but absent in 18 of 42 (43%) human prostate cancer tissues (P = 0.015). To further examine the functional role of USF2 in vivo, we generated mice with genetic deletion of USF2 gene. We found that USF2-null mice displayed marked prostate hyperplasia at a young age, suggesting that USF2 is involved in the normal growth and differentiation of prostate. Together, these studies demonstrate that USF2 has tumor-suppressor function and plays a role in prostate carcinogenesis.

Original languageEnglish (US)
Pages (from-to)579-587
Number of pages9
JournalOncogene
Volume25
Issue number4
DOIs
StatePublished - Jan 26 2006

Fingerprint

Prostate
Carcinogenesis
Transcription Factors
Neoplasms
Androgens
Prostatic Neoplasms
Growth
Epithelial Cells
Cell Proliferation
Cell Line
Gene Deletion
Heterografts
Nude Mice
Plastics
Agar
Hyperplasia
Western Blotting
Gels
Proteins

Keywords

  • Prostate cancer
  • Transcription factor
  • Tumor-suppressor gene
  • USF

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Chen, N., Szentirmay, M. N., Pawar, S. A., Sirito, M., Wang, J., Wang, Z., ... Sawadogo, M. (2006). Tumor-suppression function of transcription factor USF2 in prostate carcinogenesis. Oncogene, 25(4), 579-587. https://doi.org/10.1038/sj.onc.1209079

Tumor-suppression function of transcription factor USF2 in prostate carcinogenesis. / Chen, N.; Szentirmay, M. N.; Pawar, S. A.; Sirito, M.; Wang, J.; Wang, Z.; Zhai, Q.; Yang, H. X.; Peehl, D. M.; Ware, J. L.; Sawadogo, M.

In: Oncogene, Vol. 25, No. 4, 26.01.2006, p. 579-587.

Research output: Contribution to journalArticle

Chen, N, Szentirmay, MN, Pawar, SA, Sirito, M, Wang, J, Wang, Z, Zhai, Q, Yang, HX, Peehl, DM, Ware, JL & Sawadogo, M 2006, 'Tumor-suppression function of transcription factor USF2 in prostate carcinogenesis', Oncogene, vol. 25, no. 4, pp. 579-587. https://doi.org/10.1038/sj.onc.1209079
Chen N, Szentirmay MN, Pawar SA, Sirito M, Wang J, Wang Z et al. Tumor-suppression function of transcription factor USF2 in prostate carcinogenesis. Oncogene. 2006 Jan 26;25(4):579-587. https://doi.org/10.1038/sj.onc.1209079
Chen, N. ; Szentirmay, M. N. ; Pawar, S. A. ; Sirito, M. ; Wang, J. ; Wang, Z. ; Zhai, Q. ; Yang, H. X. ; Peehl, D. M. ; Ware, J. L. ; Sawadogo, M. / Tumor-suppression function of transcription factor USF2 in prostate carcinogenesis. In: Oncogene. 2006 ; Vol. 25, No. 4. pp. 579-587.
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