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Article

HOXB13 regulates the prostate-derived Ets factor: Implications for prostate cancer cell invasion

  • Authors:
    • In-Je Kim
    • Taek Won Kang
    • Taeoh Jeong
    • Young-Rang Kim
    • Chaeyong Jung
  • View Affiliations / Copyright

    Affiliations: Department of Anatomy, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea, Department of Urology, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea
  • Pages: 869-876
    |
    Published online on: June 3, 2014
       https://doi.org/10.3892/ijo.2014.2485
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Abstract

HOXB13 has been shown to enhance the invasive potential of breast and endometrial tumors. HOXB13 is also abundant in castration-resistant prostate tumors. To determine the invasive potential of HOXB13 in prostate tumors, highly metastatic PC3 prostate cancer cells were manipulated to express HOXB13 and/or the prostate-derived Ets factor (PDEF). The PDEF is believed to reduce the invasive potential of various tumors, including prostate tumors. To further demonstrate the functional correlation between HOXB13 and PDEF, transwell invasion and gelatin zymography assays were performed. In addition, the western blot analysis was used to demonstrate the expression of PDEF target proteins involved in cancer cell migration and invasion, MMP-9 and survivin. According to the results, HOXB13 promoted PC3 cell migration and invasion. The DNA microarray analysis demonstrated that HOXB13 significantly suppressed the expression of the PDEF. Accordingly, the expression of MMP-9 and survivin was regulated by HOXB13. In addition, HOXB13 promoted the invasive potential of PC3 cells while inhibiting the PDEF. The coexpression of HOXB13 and the PDEF led to moderate retardation of the number of invasive cells, indicating that HOXB13 functionally counteracted cell invasion by reducing PDEF expression. The western blot analysis demonstrated that HOXB13 counteracted the PDEF-mediated inhibition of the expression of PDEF target proteins such as MMP-9 and survivin. The results suggest that the HOXB13-mediated promotion of tumor cell invasion is accomplished mainly through the downregulation of PDEF expression.
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1 

Sreenath T, Orosz A, Fujita K and Bieberich CJ: Androgen-independent expression of hoxb-13 in the mouse prostate. Prostate. 41:203–207. 1999. View Article : Google Scholar : PubMed/NCBI

2 

Ma XJ, Wang Z, Ryan PD, et al: A two-gene expression ratio predicts clinical outcome in breast cancer patients treated with tamoxifen. Cancer Cell. 5:607–616. 2004. View Article : Google Scholar

3 

Miao J, Wang Z, Provencher H, et al: HOXB13 promotes ovarian cancer progression. Proc Natl Acad Sci USA. 104:17093–17098. 2007. View Article : Google Scholar : PubMed/NCBI

4 

Zhao Y, Yamashita T and Ishikawa M: Regulation of tumor invasion by HOXB13 gene overexpressed in human endometrial cancer. Oncol Rep. 13:721–726. 2005.PubMed/NCBI

5 

Edwards S, Campbell C, Flohr P, et al: Expression analysis onto microarrays of randomly selected cDNA clones highlights HOXB13 as a marker of human prostate cancer. Br J Cancer. 92:376–381. 2005. View Article : Google Scholar : PubMed/NCBI

6 

Jung C, Kim RS, Lee SJ, Wang C and Jeng MH: HOXB13 homeodomain protein suppresses the growth of prostate cancer cells by the negative regulation of T-cell factor 4. Cancer Res. 64:3046–3051. 2004. View Article : Google Scholar : PubMed/NCBI

7 

Jung C, Kim RS, Zhang HJ, Lee SJ and Jeng MH: HOXB13 induces growth suppression of prostate cancer cells as a repressor of hormone-activated androgen receptor signaling. Cancer Res. 64:9185–9192. 2004. View Article : Google Scholar : PubMed/NCBI

8 

Kim SD, Park RY, Kim YR, et al: HOXB13 is co-localized with androgen receptor to suppress androgen-stimulated prostate-specific antigen expression. Anat Cell Biol. 43:284–293. 2010. View Article : Google Scholar : PubMed/NCBI

9 

Kim YR, Oh KJ, Park RY, et al: HOXB13 promotes androgen independent growth of LNCaP prostate cancer cells by the activation of E2F signaling. Mol Cancer. 9:1242010. View Article : Google Scholar : PubMed/NCBI

10 

Kim YR, Kim IJ, Kang TW, et al: HOXB13 downregulates intracellular zinc and increases NF-kappaB signaling to promote prostate cancer metastasis. Oncogene. 7–Oct;2013.(Epub ahead of print). View Article : Google Scholar : 2013.

11 

Sharrocks AD, Brown AL, Ling Y and Yates PR: The ETS-domain transcription factor family. Int J Biochem Cell Biol. 29:1371–1387. 1997. View Article : Google Scholar : PubMed/NCBI

12 

Clark JP and Cooper CS: ETS gene fusions in prostate cancer. Nat Rev Urol. 6:429–439. 2009. View Article : Google Scholar : PubMed/NCBI

13 

Kumar-Sinha C, Tomlins SA and Chinnaiyan AM: Recurrent gene fusions in prostate cancer. Nat Rev Cancer. 8:497–511. 2008. View Article : Google Scholar : PubMed/NCBI

14 

Tomlins SA, Bjartell A, Chinnaiyan AM, et al: ETS gene fusions in prostate cancer: from discovery to daily clinical practice. Eur Urol. 56:275–286. 2009. View Article : Google Scholar : PubMed/NCBI

15 

Oettgen P, Finger E, Sun Z, et al: PDEF, a novel prostate epithelium-specific ets transcription factor, interacts with the androgen receptor and activates prostate-specific antigen gene expression. J Biol Chem. 275:1216–1225. 2000. View Article : Google Scholar : PubMed/NCBI

16 

Johnson TR, Koul S, Kumar B, et al: Loss of PDEF, a prostate-derived Ets factor is associated with aggressive phenotype of prostate cancer: regulation of MMP 9 by PDEF. Mol Cancer. 9:1482010. View Article : Google Scholar : PubMed/NCBI

17 

Gu X, Zerbini LF, Otu HH, et al: Reduced PDEF expression increases invasion and expression of mesenchymal genes in prostate cancer cells. Cancer Res. 67:4219–4226. 2007. View Article : Google Scholar : PubMed/NCBI

18 

Turner DP, Findlay VJ, Moussa O, et al: Mechanisms and functional consequences of PDEF protein expression loss during prostate cancer progression. Prostate. 71:1723–1735. 2011. View Article : Google Scholar

19 

Ghadersohi A, Pan D, Fayazi Z, Hicks DG, Winston JS and Li F: Prostate-derived Ets transcription factor (PDEF) downregulates survivin expression and inhibits breast cancer cell growth in vitro and xenograft tumor formation in vivo. Breast Cancer Res Treat. 102:19–30. 2007. View Article : Google Scholar : PubMed/NCBI

20 

Lynch CC and Matrisian LM: Matrix metalloproteinases in tumor-host cell communication. Differentiation. 70:561–573. 2002. View Article : Google Scholar : PubMed/NCBI

21 

Zhang M, Latham DE, Delaney MA and Chakravarti A: Survivin mediates resistance to antiandrogen therapy in prostate cancer. Oncogene. 24:2474–2482. 2005. View Article : Google Scholar : PubMed/NCBI

22 

Feldman RJ, Sementchenko VI, Gayed M, Fraig MM and Watson DK: PDEF expression in human breast cancer is correlated with invasive potential and altered gene expression. Cancer Res. 63:4626–4631. 2003.PubMed/NCBI

23 

Feldman RJ, Sementchenko VI and Watson DK: The epithelial-specific Ets factors occupy a unique position in defining epithelial proliferation, differentiation and carcinogenesis. Anticancer Res. 23:2125–2131. 2003.

24 

Moussa O, Turner DP, Feldman RJ, et al: PDEF is a negative regulator of colon cancer cell growth and migration. J Cell Biochem. 108:1389–1398. 2009. View Article : Google Scholar : PubMed/NCBI

25 

Turner DP, Findlay VJ, Kirven AD, Moussa O and Watson DK: Global gene expression analysis identifies PDEF transcriptional networks regulating cell migration during cancer progression. Mol Biol Cell. 19:3745–3757. 2008. View Article : Google Scholar : PubMed/NCBI

26 

Turner DP, Moussa O, Sauane M, Fisher PB and Watson DK: Prostate-derived ETS factor is a mediator of metastatic potential through the inhibition of migration and invasion in breast cancer. Cancer Res. 67:1618–1625. 2007. View Article : Google Scholar : PubMed/NCBI

27 

Schaefer JS, Sabherwal Y, Shi HY, et al: Transcriptional regulation of p21/CIP1 cell cycle inhibitor by PDEF controls cell proliferation and mammary tumor progression. J Biol Chem. 285:11258–11269. 2010. View Article : Google Scholar : PubMed/NCBI

28 

Findlay VJ, Turner DP, Yordy JS, et al: Prostate-derived ETS factor regulates epithelial-to-mesenchymal transition through both SLUG-dependent and independent mechanisms. Genes Cancer. 2:120–129. 2011. View Article : Google Scholar : PubMed/NCBI

29 

Ma XJ, Hilsenbeck SG, Wang W, et al: The HOXB13:IL17BR expression index is a prognostic factor in early-stage breast cancer. J Clin Oncol. 24:4611–4619. 2006. View Article : Google Scholar : PubMed/NCBI

30 

Ghadersohi A, Odunsi K, Zhang S, et al: Prostate-derived Ets transcription factor as a favorable prognostic marker in ovarian cancer patients. Int J Cancer. 123:1376–1384. 2008. View Article : Google Scholar : PubMed/NCBI

31 

Ghadersohi A, Sharma S, Zhang S, et al: Prostate-derived Ets transcription factor (PDEF) is a potential prognostic marker in patients with prostate cancer. Prostate. 71:1178–1188. 2011. View Article : Google Scholar : PubMed/NCBI

32 

Fromont G, Chene L, Latil A, et al: Molecular profiling of benign prostatic hyperplasia using a large scale real-time reverse transcriptase-polymerase chain reaction approach. J Urol. 172:1382–1385. 2004. View Article : Google Scholar

33 

Jeong TO, Oh KJ, Xuan Nguyen NT, et al: Evaluation of HOXB13 as a molecular marker of recurrent prostate cancer. Mol Med Rep. 5:901–904. 2012.PubMed/NCBI

34 

Johnson PH, Walker RP, Jones SW, et al: Multiplex gene expression analysis for high-throughput drug discovery: screening and analysis of compounds affecting genes overexpressed in cancer cells. Mol Cancer Ther. 1:1293–1304. 2002.PubMed/NCBI

35 

Birkenkamp-Demtroder K, Olesen SH, Sorensen FB, et al: Differential gene expression in colon cancer of the caecum versus the sigmoid and rectosigmoid. Gut. 54:374–384. 2005. View Article : Google Scholar : PubMed/NCBI

36 

Hoek K, Rimm DL, Williams KR, et al: Expression profiling reveals novel pathways in the transformation of melanocytes to melanomas. Cancer Res. 64:5270–5282. 2004. View Article : Google Scholar

37 

Jung C, Kim RS, Zhang H, et al: HOXB13 is downregulated in colorectal cancer to confer TCF4-mediated transactivation. Br J Cancer. 92:2233–2239. 2005. View Article : Google Scholar : PubMed/NCBI

38 

Komuves LG, Ma XK, Stelnicki E, Rozenfeld S, Oda Y and Largman C: HOXB13 homeodomain protein is cytoplasmic throughout fetal skin development. Dev Dyn. 227:192–202. 2003. View Article : Google Scholar : PubMed/NCBI

39 

Okuda H, Toyota M, Ishida W, et al: Epigenetic inactivation of the candidate tumor suppressor gene HOXB13 in human renal cell carcinoma. Oncogene. 25:1733–1742. 2006. View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Kim I, Kang TW, Jeong T, Kim Y and Jung C: HOXB13 regulates the prostate-derived Ets factor: Implications for prostate cancer cell invasion. Int J Oncol 45: 869-876, 2014.
APA
Kim, I., Kang, T.W., Jeong, T., Kim, Y., & Jung, C. (2014). HOXB13 regulates the prostate-derived Ets factor: Implications for prostate cancer cell invasion. International Journal of Oncology, 45, 869-876. https://doi.org/10.3892/ijo.2014.2485
MLA
Kim, I., Kang, T. W., Jeong, T., Kim, Y., Jung, C."HOXB13 regulates the prostate-derived Ets factor: Implications for prostate cancer cell invasion". International Journal of Oncology 45.2 (2014): 869-876.
Chicago
Kim, I., Kang, T. W., Jeong, T., Kim, Y., Jung, C."HOXB13 regulates the prostate-derived Ets factor: Implications for prostate cancer cell invasion". International Journal of Oncology 45, no. 2 (2014): 869-876. https://doi.org/10.3892/ijo.2014.2485
Copy and paste a formatted citation
x
Spandidos Publications style
Kim I, Kang TW, Jeong T, Kim Y and Jung C: HOXB13 regulates the prostate-derived Ets factor: Implications for prostate cancer cell invasion. Int J Oncol 45: 869-876, 2014.
APA
Kim, I., Kang, T.W., Jeong, T., Kim, Y., & Jung, C. (2014). HOXB13 regulates the prostate-derived Ets factor: Implications for prostate cancer cell invasion. International Journal of Oncology, 45, 869-876. https://doi.org/10.3892/ijo.2014.2485
MLA
Kim, I., Kang, T. W., Jeong, T., Kim, Y., Jung, C."HOXB13 regulates the prostate-derived Ets factor: Implications for prostate cancer cell invasion". International Journal of Oncology 45.2 (2014): 869-876.
Chicago
Kim, I., Kang, T. W., Jeong, T., Kim, Y., Jung, C."HOXB13 regulates the prostate-derived Ets factor: Implications for prostate cancer cell invasion". International Journal of Oncology 45, no. 2 (2014): 869-876. https://doi.org/10.3892/ijo.2014.2485
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