title: HOXB13 regulates the prostate-derived Ets factor: implications for prostate cancer cell invasion.
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.
authors.affiliation: Department of Anatomy, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea.
authors.forename: In-Je
authors.initials: IJ
authors.lastname: Kim
authors.affiliation: Department of Urology, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea.
authors.forename: Taek Won
authors.initials: TW
authors.lastname: Kang
authors.affiliation: Department of Anatomy, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea.
authors.forename: Taeoh
authors.initials: T
authors.lastname: Jeong
authors.affiliation: Department of Anatomy, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea.
authors.forename: Young-Rang
authors.initials: YR
authors.lastname: Kim
authors.affiliation: Department of Anatomy, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea.
authors.forename: Chaeyong
authors.initials: C
authors.lastname: Jung
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D050783:Proto-Oncogene Proteins c-ets / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: C484414:HOXB13 protein, human; D018398:Homeodomain Proteins; D050783:Proto-Oncogene Proteins c-ets; C403974:SPDEF protein, human