Tumour‐suppressor genes in prostatic oncogenesis: a positional approach

Bookstein, Robert; Bova, G. Steven; MacGrogan, Donal; Levy, Alina; Isaacs, William B.

doi:10.1111/j.1464-410x.1997.tb00798.x

Cited by 55 publications

(33 citation statements)

References 45 publications

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“…Chromosomal region 8p22 contains the known putative TSGs MSR1 and N33. 22,23 He et al 24 mapped the NKX3.1 gene to 8p21, which is a human prostate-specific, androgen-regulated homeobox gene. Many studies indicate that loss of 8p12-21 is an early event in prostate carcinogenesis, whereas loss of 8p22 is a later event that is common in advanced prostate cancers.…”

Section: Chromosomal Lossesmentioning

confidence: 99%

Genetic changes in pT2 and pT3 prostate cancer detected by comparative genomic hybridization

Fukasawa

Kino

Kobayashi

et al. 2007

Prostate Cancer Prostatic Dis

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Prostate-specific antigen (PSA) screening has led to a remarkable increase in prostate cancer cases undergoing operative therapy. Over half of patients with locally advanced cancer (^pT3) develop rising PSA levels (biochemical failure) within 10 years. It is very difficult to predict which patients will progress rapidly to advanced disease following biochemical failure (BF). Therefore, a more useful prognostic factor is needed to suggest the most appropriate therapies for each patient. To determine chromosomal aberrations, we examined 30 patients with stage pT2 or pT3 primary prostate adenocarcinomas and no metastases (pN0M0) by comparative genomic hybridization (CGH). Laser capture microdissection (LCM) was used to gather cancer cells from frozen prostate specimens. Common chromosomal alterations included losses on 2q23-24, 4q26-28, 6q14-22, 8p12-22 and 13q21-31, as well as gains on 1p32-36, 6p21 and 17q21-22. Losses at 8p12-22 and 13q21-31 were observed more frequently in pT3 than pT2 tumors (Po0.05 and Po0.01, respectively). Losses at 8p12-22 were more frequent in tumors with BF (Po0.05), and those at 13q12-21 were more frequent in tumors with Gleason score (GS) 7 or more than lower GS (Po0.05). These findings suggest that losses of 8p12-22 and 13q21-31 are important determinants of prostate cancer progression.

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Section: Chromosomal Lossesmentioning

confidence: 99%

Genetic changes in pT2 and pT3 prostate cancer detected by comparative genomic hybridization

Fukasawa

Kino

Kobayashi

et al. 2007

Prostate Cancer Prostatic Dis

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“…This viral vector system will be very useful for prostate cancer, because mutation or deletion of the p53 genes can be detected in approximately 50% of all advanced -stage prostate cancers. 19,20 In the field of cancer gene therapy using viral vectors, it is very difficult, perhaps impossible, to introduce a foreign gene into all target cells. Therefore adjacent cell killing, the so-called bystander effect, caused by genetically modified cells provides therapeutic advantages for gene therapy against cancers.…”

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confidence: 99%

Replicating adenoviral vector–mediated transfer of a heat-inducible double suicide gene for gene therapy

Battle

et al. 2001

Cancer Gene Ther

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Tumor cells that express a fusion gene of Escherichia coli cytosine deaminase ( CD ) and herpes simplex virus type 1 thymidine kinase ( TK ) sequences activate and are subsequently killed by the nontoxic prodrugs 5 -fluorocytosine and ganciclovir. We have previously developed a recombinant adenovirus containing the CD -TK fusion gene controlled by the human inducible heat shock protein 70 promoter so that heat at 418C for 1 hour induces therapeutic gene expression. This adenovirus effectively transduces heat -inducible expression of the CD -TK gene into human prostate carcinoma cells. However, because a limited number of cells in a tumor can actually be infected, we created a replicating adenoviral vector to increase CD -TK gene expression. This vector is a replication -competent, E1B -attenuated adenoviral vector containing the hsp70 promoter ± driven CD -TK gene ( Ad.E1A( + )HS -CDTK ). When human prostate adenocarcinoma DU -145 cells ( mutant p53 ) were infected with the virus at a multiplicity of infection ( MOI ) of 1 or 10, the viral replication was detected within 2 days at both MOIs. Similar results were observed in human colorectal carcinoma CX -1 cells. When DU -145 cells were infected with the virus at an MOI of 10, incubated for 24 hours, heated at 418C for 4 hours, and then harvested 20 hours later, Western blot analysis demonstrated that this virus successfully produced viral E1A proteins and heat shock stimulated the CD -TK gene expression by 12.3 -fold. In addition, Ad.E1A( + )HS -CDTK effectively suppressed cell proliferation by viral cytopathic effect ). Unlike with a replication -incompetent virus ( Ad.HS -CDTK ), the cytopathic effect of the virus and cytotoxicity in the presence of the prodrugs were still observed even at low MOI ( MOI = 1.0 ). Cancer Gene Therapy ( 2001 ) 8, 397 ± 404

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“…A role of HER-2/neu is not certain (Kuhn et al, 1993;Sadasivan et al, 1993). Recent evidence suggests that tumoursuppressor genes (TSGs) might be more important for the development of prostate carcinoma (Bookstein, 1994;Isaacs, 1995). Mutations and allelic losses (loss of heterozygosity or LOH) have been demonstrated for TSGs such as TP53 (Gao et al, 1995a), DCC (deleted in colon carcinoma) (Gao et al, 1993), APC (adenomatous polyposis coli), MCC (mutated in colorectal cancer) (Gao et al, 1995b), E-cadherin (Umbas et al, 1992) and BRCA1 (breast carcinoma-associated gene) (Gao et al, 1995c).…”

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confidence: 99%

Loss of heterozygosity (LOH), malignancy grade and clonality in microdissected prostate cancer

Hügel

Wernert

1999

Br J Cancer

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SummaryThe aim of the present study was to find out whether increasing malignancy of prostate carcinoma correlates with an overall increase of loss of heterozygosity (LOH), and whether LOH typing of microdissected tumour areas can help to distinguish between multifocal or clonal tumour development. In 47 carcinomas analysed at 25 chromosomal loci, the overall LOH rate was found to be significantly lower in grade 1 areas (2.2%) compared with grade 2 (9.4%) and grade 3 areas (8.3%, P = 0.007). A similar tendency was found for the mean fractional allele loss (FAL, 0.043 for grade 1, 0.2 for grade 2 and 0.23 for grade 3, P = 0.0004). Of 20 tumours (65%) with LOH in several microdissected areas, 13 had identical losses at 1-4 loci within two or three areas, suggesting clonal development of these areas. Markers near RB, DCC, BBC1, TP53 and at D13S325 (13q21-22) showed higher loss rates in grades 2 and 3 (between 25% and 44.4%) compared with grade 1 (0-6.6%). Tumour-suppressor genes (TSGs) near these loci might, thus, be important for tumour progression. TP53 mutations were detected in 27%, but BBC1 mutations in only 7%, of samples with LOH. Evaluation of all 25 loci in every tumour made evident that each prostate cancer has its own pattern of allelic losses.

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Tumour‐suppressor genes in prostatic oncogenesis: a positional approach

Cited by 55 publications

References 45 publications

Genetic changes in pT2 and pT3 prostate cancer detected by comparative genomic hybridization

Genetic changes in pT2 and pT3 prostate cancer detected by comparative genomic hybridization

Replicating adenoviral vector–mediated transfer of a heat-inducible double suicide gene for gene therapy

Loss of heterozygosity (LOH), malignancy grade and clonality in microdissected prostate cancer

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