BACKGROUND: Three-dimensional culture (3DC) is a relevant in vitro model used to study prostate development and carcinogenesis. Recent studies have indicated that 3DC-associated genes would be more sensitive as prognostic markers for cancer; however, no 3DC-associated genes in prostate cancer (CaP) have thus far been elucidated. METHODS: Candidate 3DC-associated genes in non-malignant prostatic epithelial cells, RWPE-1 and TA2, were selected, based on a comparison of microarray gene expression data between cells grown in two-dimensional culture (2DC) and in 3DC. To extract CaP-associated genes among the 3DC-associated genes, gene expression levels from the microdissected tissue samples were compared between 20 well-differentiated or 20 poorly differentiated CaP, as well as matched normal prostate epithelium. The expression levels of CaP-associated genes in 3DC were validated by quantitative RT-PCR using TA2 cells in 2DC and 3DC. Protein expression of periostin (POSTN), which is one of the 3DC CaP-associated genes, was further evaluated in the clinical samples by immunohistochemistry. RESULTS: Several genes including POSTN were identified as CaP-associated genes using a 3DC system. Immunohistochemical analyses revealed that POSTN expression was increased in the early stages of CaP (Gleason score 6-7), but not in the advanced stages of CaP. Furthermore, the positive ratio observed for the expression of POSTN in tumor-associated stroma was significantly correlated with the degree of malignancy. CONCLUSIONS: POSTN, one of the 3DC-associated genes, may serve as a potential biomarker for predicting the pathological grade and prognosis of CaP. Prostate 69: 1398-1403, 2009. (c) 2009 Wiley-Liss, Inc.
BACKGROUND: Three-dimensional culture (3DC) is a relevant in vitro model used to study prostate development and carcinogenesis. Recent studies have indicated that 3DC-associated genes would be more sensitive as prognostic markers for cancer; however, no 3DC-associated genes in prostate cancer (CaP) have thus far been elucidated. METHODS: Candidate 3DC-associated genes in non-malignant prostatic epithelial cells, RWPE-1 and TA2, were selected, based on a comparison of microarray gene expression data between cells grown in two-dimensional culture (2DC) and in 3DC. To extract CaP-associated genes among the 3DC-associated genes, gene expression levels from the microdissected tissue samples were compared between 20 well-differentiated or 20 poorly differentiated CaP, as well as matched normal prostate epithelium. The expression levels of CaP-associated genes in 3DC were validated by quantitative RT-PCR using TA2 cells in 2DC and 3DC. Protein expression of periostin (POSTN), which is one of the 3DC CaP-associated genes, was further evaluated in the clinical samples by immunohistochemistry. RESULTS: Several genes including POSTN were identified as CaP-associated genes using a 3DC system. Immunohistochemical analyses revealed that POSTN expression was increased in the early stages of CaP (Gleason score 6-7), but not in the advanced stages of CaP. Furthermore, the positive ratio observed for the expression of POSTN in tumor-associated stroma was significantly correlated with the degree of malignancy. CONCLUSIONS:POSTN, one of the 3DC-associated genes, may serve as a potential biomarker for predicting the pathological grade and prognosis of CaP. Prostate 69: 1398-1403, 2009. (c) 2009 Wiley-Liss, Inc.