Differential gene expression in the peripheral zone compared to the transition zone of the human prostate gland

Noël, Elodie; Ragavan, Narasimhan; James, Sarah‐Naomi; Matanhelia, Shyam S.; Nicholson, C. M.; Lu, Yong‐Jie; Martin, Francis L.

doi:10.1038/sj.pcan.4500997

Cited by 17 publications

(26 citation statements)

References 27 publications

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“…Previous studies have explored potential differences between the zones of the prostate, and found that indeed the different zones of the prostate possess distinct gene expression profiles that might be responsible for their diverse clinical behaviors. 19,20 Hyperplastic growth of the prostate transition zone associated with clinical benign prostatic hyperplasia may be the result of the abnormal expression of key androgen-responsive genes, which lead to an imbalance between cell division and death. 44 Genes regulated by androgenic hormones are of critical importance for the normal physiological function of the human prostate gland, and they contribute to the development and progression of prostate carcinoma.…”

Section: Discussionmentioning

confidence: 99%

“…14 Morphologic and molecular differences between cancers arising from different zones of the prostate gland have been described. [15][16][17][18][19][20] All these studies have shown that transition zone tumors may have a different histogenesis, less malignant potential, and, consequently, a more indolent natural history. Recently, transition zone tumors and cancers arising in the most anterior horns of the peripheral zone have been further characterized and grouped together under the designation of 'anterior-predominant prostatic tumors,' to be distinguished from those arising in the posterior peripheral zone.…”

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confidence: 99%

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ERG rearrangement is present in a subset of transition zone prostatic tumors

et al. 2010

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A majority of prostate cancers exhibit a recurrent gene rearrangement involving chromosome 21. In approximately 90% of cases, the rearrangement is characterized by fusion of the androgen-regulated gene TMPRSS2 with the oncogene ERG. A recent study suggested that TMPRSS2-ERG gene fusion is lacking in cancers arising from the transition zone of the prostate. A dominant transition zone cancer was detected in 62/397 (16%) patients who underwent radical prostatectomy at our institution and were reviewed and mapped by a single pathologist. In 46/62 specimens, a secondary tumor was identified in the peripheral zone of the prostate. A tissue microarray containing both transition and peripheral zone tumors was constructed and evaluated for gene fusion analysis. TMPRSS2-ERG fusion status was determined using a multicolor interphase fluorescence in situ hybridization assay for ERG break-apart. The median age of the patients was 59 years. Prostatectomy Gleason score was 6 in 21, 7 in 34, and Z8 in 7 cases. Median tumor volume was 200 mm 2 . TMPRSS2-ERG gene fusion was present in 7/59 (12%) transition zone, and in 12/35 (34%) peripheral zone tumors. Transition zone fusion-positive cases were larger than their negative counterparts. No significant correlation was found between fusion status and Gleason score or pathologic stage. Gene fusion through deletion occurred in 4/7 transition zone and 7/12 peripheral zone tumors. Transition zone prostate cancers are considered biologically and genetically different from peripheral zone tumors. Although ERG rearrangement is more common in peripheral zone tumors, we have detected TMPRSS2-ERG fusion in a subset of transition zone cancers (12%). The lower frequency of gene fusion in transition zone prostate cancer may suggest distinct molecular alterations from peripheral zone tumors and the association with a high tumor volume may indicate a growth advantage for transition zone tumors harboring the gene fusion. Further studies are necessary to confirm this hypothesis.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

ERG rearrangement is present in a subset of transition zone prostatic tumors

et al. 2010

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“…Gene expression profiling using cDNA microarray techniques have shown that hundreds of genes have different expression levels in transition zone and peripheral zone tumors. 14,15 Compared with peripheral zone tumors, transition zone tumors have a low proliferation rate and low microvessel density. 16 In addition, transition zone tumors also express lower levels of p53 and bcl-2 than peripheral zone tumors.…”

Section: Discussionmentioning

confidence: 99%

“…[10][11][12][13] Some studies have suggested that there are differential expression levels of proliferative genes and oncogenes between transition and peripheral zone tumors, which may contribute to their clinical and biological differences. [14][15][16][17] However, to our knowledge, the role of TMPRSS2-ERG gene fusion in the zonal origin of prostate cancer has not been studied. In this study, we evaluated the TMPRSS2-ERG gene fusion in prostate cancers arising from the transition zone in comparison with those arising from the peripheral zone.…”

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Prostate cancer of transition zone origin lacks TMPRSS2–ERG gene fusion

et al. 2009

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Recent studies have shown a unique chromosomal rearrangement that leads to the fusion of 5 0 -transmembrane protein serine proteinase-2 (TMPRSS2) with the EST-related gene (ERG) in prostate cancer. In this study, we used fluorescence in situ hybridization to evaluate TMPRSS2-ERG gene fusion in prostate cancer of different zonal origins. Radical prostatectomy specimens with multifocal prostate cancer were obtained from 30 patients who were treated at our institution. Two separate tumor foci in each specimen, one in the peripheral zone and the other in the transition zone, were selected for gene fusion analysis. The selected peripheral zone tumor foci had a mean Gleason score of 6.8 (range, 6-7) and a mean tumor volume of 1.2 cm 3 (range, 0.1-4.6 cm 3 ). The selected transition zone tumor foci had a mean Gleason score of 6.7 (range, 5-8) and a mean tumor volume of 4.0 cm 3 (range, 0.5-9.0 cm 3 ). ERG gene rearrangement was not observed in any transition zone tumors; however, it was found in the peripheral zone tumors in 13 cases (43%). In 10 cases, the rearrangement was associated with the deletion of the 5 0 -end of ERG. In conclusion, we found that TMPRSS2-ERG gene fusion is associated with the zonal origin of prostate cancer. This gene fusion is prevalent in prostate cancer arising from the peripheral zone, but is lacking in prostate cancer arising from the transition zone.

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“…Several studies have shown that the expression of certain genes differs between these two zones. [5][6][7][8][9] Feneley et al 10 reported that the epithelial content was significantly greater in the TZ than in the PZ. Conversely, concentrations of androgen receptor (AR) activity were higher in the PZ epithelium than in the TZ epithelium, but higher concentrations of oestrogen receptor activity were detected in the TZ zone stroma.…”

Section: Introductionmentioning

confidence: 99%

The differential effects of prostate stromal cells derived from different zones on prostate cancer epithelial cells under the action of sex hormones

Jiang

Han²,

Zhao³

et al. 2011

Asian J Androl

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It is well known that prostate cancer (PCa) occurs predominantly in the peripheral zone (PZ), whereas benign prostatic hyperplasia (BPH) typically develops in the transition zone. To identify possible mechanisms underlying zonal differences, we compared the effects of prostate stromal cells derived from the peripheral zone (PZsc) and the transition zone (TZsc) on a PCa epithelial cell line (PC3) in the presence of sex hormones. First, we observed that androgen receptor (AR) mRNA was more highly expressed in PZsc than TZsc when the cells were treated with dihydrotestosterone (DHT) and b-oestradiol (E2) (P,0.05). By ELISA, we looked for differences in the secretion of peptide growth factors from PZsc and TZsc. We found that keratinocyte growth factor (KGF) secretion increased with increasing concentrations of DHT (P,0.01) and was higher in PZsc than TZsc. Under treatment with DHT plus E2, PZsc secreted more transforming growth factor-b1 (TGF-b1) than TZsc, but this pattern was reversed when the cells were treated with E2 only. With increasing concentrations of DHT, insulin-like growth factor-1 (IGF-1) secretion increased in PZsc but decreased in TZsc. To further characterize the effects of PZsc and TZsc on PC3 cells, we developed a coculture model and performed MTT assays, Western blot analysis and real-time RT-PCR. We found that PZsc promoted PC3 cell proliferation and progression better than TZsc, particularly when treated with 10 nmol l 21 DHT plus 10 nmol l 21 E2. In conclusion, our data suggest that PZsc may have a greater capacity to induce PCa development and progression than TZsc via growth factors regulated by sex hormones. These findings provide possible mechanisms underlying zonal differences in prostate diseases, which may aid the search for novel therapeutic targets for PCa.

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Differential gene expression in the peripheral zone compared to the transition zone of the human prostate gland

Cited by 17 publications

References 27 publications

ERG rearrangement is present in a subset of transition zone prostatic tumors

ERG rearrangement is present in a subset of transition zone prostatic tumors

Prostate cancer of transition zone origin lacks TMPRSS2–ERG gene fusion

The differential effects of prostate stromal cells derived from different zones on prostate cancer epithelial cells under the action of sex hormones

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