Expression of pi-class glutathione S-transferase: two populations of high grade prostatic intraepithelial neoplasia with different relations to carcinoma

Montironi, Rodolfo; Mazzucchelli, Roberta; Stramazzotti, Daniela; Pomante, Roberto; Thompson, Deborah; Ph, Bartels

doi:10.1136/mp.53.3.122

Cited by 22 publications

(15 citation statements)

References 33 publications

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“…Among these genes were some known to relate to prostate cancers, such as prostate-speci®c membrane antigen (FOLH1) [7,8] and glutathione-Stransferase pi (GST-pi) [9]. Most of the sequences in the list (Table 1), however, were novel in terms of their relationship to prostate cancers.…”

Section: Resultsmentioning

confidence: 96%

Gene expression analysis of prostate cancers

Luo

Cieply

et al. 2002

Molecular Carcinogenesis

217

120

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Prostate cancer is a biologically heterogeneous disease with considerable variation in clinical aggressiveness. The behavior of prostate cancer can be considered a direct or indirect result of aberrant alterations of gene expression in prostate epithelial cells. Identification of the patterns of gene-expression alterations that are related to the aggressiveness of prostate cancers will greatly assist the development of tools for early detection of prostate cancers with poor clinical outcome and identification of targets for future therapeutic intervention. To detect the patterns of gene-expression alterations of prostate cancers, we performed a comprehensive gene-expression analysis on 30 prostate tissues of various levels of invasiveness (ranging from those confined to the organ to distant metastases) and Gleason grades (combined scores 4-9), using the Affymetrix chip set Hu35k (A-D) and U95a. Following three sequential selection screens, we identified 84 largely novel genes and expressed sequence tag (EST) sequences whose expression levels were altered significantly in prostate cancer samples compared with control normal tissues. In addition, the expression levels of a group of 12 genes and EST sequences was found to be altered significantly in aggressive type of prostate cancers but not in organ-confined prostate cancers. Cluster analysis using the 84-gene list showed that the highly aggressive prostate cancers contained gene-expression patterns that were distinct from organ-confined prostate cancers.

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Section: Resultsmentioning

confidence: 96%

Gene expression analysis of prostate cancers

Luo

Cieply

et al. 2002

Molecular Carcinogenesis

217

120

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“…Among these conditions, high-grade PIN stands as the most likely and well-documented prostatic precancerous lesion (2), preceding at times by several decades the development of invasive prostate cancer (3). Indeed, several studies suggested that highgrade PIN is more closely related to prostate carcinoma than normal prostate tissue (4,5). Moreover, high-grade PIN lesions, like prostate carcinomas, display considerable genetic heterogeneity as revealed by loss of heterozygozity, fluorescence in situ hybridization, gene expression profiling, and comparative genomic hybridization studies (6)(7)(8)(9)(10)(11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

Epigenetic Heterogeneity of High-Grade Prostatic Intraepithelial Neoplasia: Clues for Clonal Progression in Prostate Carcinogenesis

Henrique

Jerónimo

Teixeira

et al. 2006

Molecular Cancer Research

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High-grade prostatic intraepithelial neoplasia (PIN) is the most likely precursor of prostate adenocarcinoma, but the frequency and timing of epigenetic changes found in prostate carcinogenesis has not been extensively documented. Thus, the promoters of three genes (APC, GSTP1, and RARb2) involved in prostate carcinogenesis were tested by quantitative methylation-specific PCR in tissue DNA from 30 prostate carcinomas, 128 high-grade PIN lesions, and 30 normal prostate tissue samples dissected from 30 radical prostatectomy specimens using laser capture microdissection. The percentage of methylated alleles (PMA) was calculated for each gene, and hierarchical cluster analysis was used to define the degree of similarity of epigenetic alterations among the various samples. We found that PMA values of APC and RARb2 were higher than those of GSTP1 in all three types of tissue samples and median PMA values for all three genes were higher in prostate cancer. By cluster analysis, 26 of 30 prostate carcinomas and 82 of 128 high-grade PIN lesions were grouped in the ''high methylation'' branch, whereas 24 of 30 normal prostate tissue samples were allocated in the ''low methylation'' branch. Although high-grade PIN lesions are epigenetically more similar to prostate carcinoma than to normal prostate tissue, paired prostate carcinoma and high-grade PIN lesions did not always segregate together. We concluded that APC and RARb2 hypermethylation is frequent in normal prostate tissue and the progressive enrichment in cells carrying methylated alleles observed in high-grade PIN and prostate carcinoma is consistent with clonal progression. Because GSTP1 promoter methylation is mainly observed in prostate carcinoma and some high-grade PIN lesions, it represents an important marker for the transition of in situ to invasive neoplasia.

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“…Although ATIP immunostaining was low or not detected in either the basal or columnar epithelial cell layers surrounding BPH glands, it was routinely observed in the neoplastic epithelial cells of HGPIN and in the cytoplasms of the malignant cells in all grades of prostate cancer (Figures 3 and 4). HGPIN is considered to be a precursor to prostate cancer [14,15] as it possesses most of the phenotypic, biochemical and genetic changes of cancer without invasion of the basement membrane of the acini [16]. The up-regulation of ATIP in neoplastic cells in HGPIN and its continued presence in cancer adds further support to the notion that malignant prostatic cells arise from the neoplastic epithelial cells of HGPIN [13].…”

Section: Resultsmentioning

confidence: 99%

The Expression of MTUS1/ATIP and Its Major Isoforms, ATIP1 and ATIP3, in Human Prostate Cancer

Louis

Chow

Varghayee

et al. 2011

Cancers

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Angiotensin II (Ang II), the main effector of the renin angiotensin system, acts upon two distinct transmembrane receptors, the Ang II type 1 and the type 2 (AT2-) receptor, to induce promotion and inhibition of ERK2 phosphorylation. The AT2-receptor, through an interaction with its putative signaling partner MTUS1/ATIP (AT2-receptor interacting protein), inhibits the mitogenic effects of EGF in prostate cancer cell lines representing both early and late stage disease. This is the first report on the expression of ATIP in normal and malignant human prostatic biopsies. The expression of ATIP and its major isoforms, ATIP1 and ATIP3, in normal prostatic cells and three prostate cancer cell lines was examined using QPCR and immunohistochemistry. Human biopsies containing benign prostatic hyperplasia (BPH), high grade prostatic intraepithelial neoplasia (HGPIN) and well, moderately and poorly differentiated prostate cancer were also examined. Overall, ATIP1 and ATIP3 mRNA expression was increased in malignant compared to normal tissues and cell lines. ATIP immunostaining was low or absent in both the basal and columnar epithelial cell layers surrounding BPH acini; however, it was observed in high concentration in neoplastic epithelial cells of HGPIN and was clearly evident in cytoplasms of malignant cells in all prostate cancer grades. ATIP immunostaining was also identified in the cytoplasms of LNCaP and PC3 prostate cancer cells. As the AT2-receptor/ATIP inhibitory signaling pathway exists in malignant cells in all grades of prostate cancer, enhancement of this pathway may be a therapeutic target even after the development of androgen-independence.

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Expression of pi-class glutathione S-transferase: two populations of high grade prostatic intraepithelial neoplasia with different relations to carcinoma

Cited by 22 publications

References 33 publications

Gene expression analysis of prostate cancers

Gene expression analysis of prostate cancers

Epigenetic Heterogeneity of High-Grade Prostatic Intraepithelial Neoplasia: Clues for Clonal Progression in Prostate Carcinogenesis

The Expression of MTUS1/ATIP and Its Major Isoforms, ATIP1 and ATIP3, in Human Prostate Cancer

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