Project description:BACKGROUND: Prostate cancer is the most frequently diagnosed cancer among men in the United States. In contrast, cancer of the seminal vesicle is exceedingly rare, despite that the prostate and seminal vesicle share similar histology, secretory function, androgen dependency, blood supply, and (in part) embryonic origin. We hypothesized that gene-expression differences between prostate and seminal vesicle might inform mechanisms underlying the higher incidence of prostate cancer. METHODS: Whole-genome DNA microarrays were used to profile gene expression of 11 normal prostate and 7 seminal vesicle specimens (including 6 matched pairs) obtained from radical prostatectomy. Supervised analysis was used to identify genes differentially expressed between normal prostate and seminal vesicle, and this list was then cross-referenced to genes differentially expressed between normal and cancerous prostate. Expression patterns of selected genes were confirmed by immunohistochemistry using a tissue microarray. We identified 32 genes that displayed a highly statistically-significant expression pattern with highest levels in seminal vesicle, lower levels in normal prostate, and lowest levels in prostate cancer. Among these genes was the known candidate prostate tumor suppressor GSTP1 (involved in xenobiotic detoxification). The expression pattern of GSTP1 and four other genes, ABCG2 (xenobiotic transport), CRABP2 (retinoic acid signaling), GATA3 (lineage-specific transcription) and SLPI (immune response), was confirmed by immunohistochemistry. CONCLUSIONS: Our findings identify candidate prostate cancer genes whose reduced expression in prostate (compared to seminal vesicle) may be permissive to prostate cancer initiation. Such genes and their pathways may inform mechanisms of prostate carcinogenesis, and suggest new opportunities for prostate cancer prevention. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Disease State: normal prostate vs normal seminal vesicle sample Individual Keywords: Logical Set cDNA microarrays from the Stanford Functional Genomics Facility were used for expression profiling of 11 normal prostate and 7 seminal vesicle specimens (6 of which were matched pairs), against a universal RNA reference. Extracted expression ratios were normalized by array then mean centered by gene, and expression differences between normal prostate and seminal vesicle identified using Significance Analysis of Microarrays (SAM).
Project description:BACKGROUND: Prostate cancer is the most frequently diagnosed cancer among men in the United States. In contrast, cancer of the seminal vesicle is exceedingly rare, despite that the prostate and seminal vesicle share similar histology, secretory function, androgen dependency, blood supply, and (in part) embryonic origin. We hypothesized that gene-expression differences between prostate and seminal vesicle might inform mechanisms underlying the higher incidence of prostate cancer. METHODS: Whole-genome DNA microarrays were used to profile gene expression of 11 normal prostate and 7 seminal vesicle specimens (including 6 matched pairs) obtained from radical prostatectomy. Supervised analysis was used to identify genes differentially expressed between normal prostate and seminal vesicle, and this list was then cross-referenced to genes differentially expressed between normal and cancerous prostate. Expression patterns of selected genes were confirmed by immunohistochemistry using a tissue microarray. We identified 32 genes that displayed a highly statistically-significant expression pattern with highest levels in seminal vesicle, lower levels in normal prostate, and lowest levels in prostate cancer. Among these genes was the known candidate prostate tumor suppressor GSTP1 (involved in xenobiotic detoxification). The expression pattern of GSTP1 and four other genes, ABCG2 (xenobiotic transport), CRABP2 (retinoic acid signaling), GATA3 (lineage-specific transcription) and SLPI (immune response), was confirmed by immunohistochemistry. CONCLUSIONS: Our findings identify candidate prostate cancer genes whose reduced expression in prostate (compared to seminal vesicle) may be permissive to prostate cancer initiation. Such genes and their pathways may inform mechanisms of prostate carcinogenesis, and suggest new opportunities for prostate cancer prevention. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Disease State: normal prostate vs normal seminal vesicle sample Individual Keywords: Logical Set
Project description:To investigate the identity of the tissue origin for metastases, we compared gene expression profiles of the prostate tissues and seminal vesicles from PB-Pten-NICD mice and those of 7 lung metastases from different mice. Three respective cell lines established from primary seminal vesicle tumors, primary prostate tumors, and lung metastases in PB-Pten-NICD mice were also included in the microarray analysis. We hypothesized that the gene expression profiles of primary and metastatic tumors should resemble those of their tissue origins. We identified genes differentially expressed between the seminal vesicle and prostate tumors. The expression profiles of the two cell lines established from primary tumors resembled those of their respective tissue origins, which supports our hypothesis. The expression profile of the metastatic cell line resembled those of the prostate tumor tissues, indicating the prostate as its tissue of origin. The expression profiles of 2 metastatic specimens each resembled those of the seminal vesicle tumors and the prostate tumors, respectively, while the expression profiles of the remaining 3 samples displayed a mixed pattern. This study suggests that metastatic tumors in this model may have originated from either the prostate, or the seminal vesicles, or both.
Project description:Mechanistic links between development and disease can be exploited to provide clues to the cellular signalling pathways that might become re-activated during adult pathogenesis such as those affecting the prostate. However, the mechanisms underpinning prostate development require further characterisation. Previously, our group developed novel methods to produce prostate organoids using induced pluripotent stem cells (iPSCs). Here, we show that the iPSCs can be fully differentiated into prostate organoids using neonatal rodent seminal vesicle mesenchyme (SVM) in vitro. Additionally, we elucidated molecular drivers of prostate induction through RNA-sequencing analyses of the rat urogenital sinus (the embryonic precursor of the prostate gland) as well as the neonatal seminal vesicles. We identified candidate drivers evident in the inductive mesenchyme and epithelium involved with prostate specification. Our top candidates included Spx, Trib3, Snai1, Snai2, Nrg2, and Lrp4. This work lays the foundations to further interrogate the reactivation of developmental genes in adulthood, leading to prostate disease.
Project description:To investigate the role of NKX3.1 in prostate differentiation, we employed transcriptome analysis of mouse seminal vesicle (from 15-month-old Nkx3.1+/+ mice); mouse prostate (from 4-month-old Nkx3.1+/+ and Nkx3.1-/- mice); human prostate cells (RWPE1 cells engineered with empty vector (altered pTRIPZ), NKX3.1 wild type over-expression, and NKX3.1 (T164A) mutant over-expression); and tissue recombinants (generated from combining engineered mouse epithelial cells (seminal vesicle epithelial cells or prostate epithelial cells from 2-month-old mice) and rat UGS mesenchymal cells). Mouse tissue or human cells were snap frozen for subsequent molecular analysis. This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
Project description:To investigate the role of NKX3.1 in prostate differentiation, we employed transcriptome analysis of mouse seminal vesicle (from 15-month-old Nkx3.1+/+ mice); mouse prostate (from 4-month-old Nkx3.1+/+ and Nkx3.1-/- mice); human prostate cells (RWPE1 cells engineered with empty vector (altered pTRIPZ), NKX3.1 wild type over-expression, and NKX3.1 (T164A) mutant over-expression); and tissue recombinants (generated from combining engineered mouse epithelial cells (seminal vesicle epithelial cells or prostate epithelial cells from 2-month-old mice) and rat UGS mesenchymal cells). Mouse tissue or human cells were snap frozen for subsequent molecular analysis. This SuperSeries is composed of the SubSeries listed below.
Project description:Analysis of transcriptome of tissue recombinants (mouse seminal vesicle epithelial [SVE] cells or prostate epithelial [PE] cells, and rat urogenital sinus [UGS] mesenchymal cells) grown under the kidney capsule in athymic nude mice for 3 months.
Project description:From over 300 patients two groups were selected which had prostate tumors with either well differentiated (WD) or poorly differentiated (PD) after radical Prostatectomy. The PD group had Gleason score 8-9, seminal vesicle invasion, and poorly differentiated tumor cells; the WD group had Gleason score 6-7, no seminal vesicle invasion, and well to moderately differentiated tumor cells. LCM compatible specimens were selected from age and race (Caucasians) matched PD or WD patients with no family history of CaP. Matching normal epithelal cells were also selected for the analysis.
Project description:From over 300 patients two groups were selected which had prostate tumors with either well differentiated (WD) or poorly differentiated (PD) after radical Prostatectomy. The PD group had Gleason score 8-9, seminal vesicle invasion, and poorly differentiated tumor cells; the WD group had Gleason score 6-7, no seminal vesicle invasion, and well to moderately differentiated tumor cells. LCM compatible specimens were selected from age and race (Caucasians) matched PD or WD patients with no family history of CaP. Matching normal epithelal cells were also selected for the analysis. From 40 patients specimens were obtained under an IRB-approved protocol from patients treated with radical prostatectomy (RP) at Walter Reed Army Medical Center (WRAMC).