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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A procedure is described to discover genes that are specifically expressed in human prostate. The procedure involves searching the expressed sequence tag (EST) database for genes that have many related EST sequences from human prostate cDNA libraries but none or few from nonprostate human libraries. The selected candidate EST clones were tested by RNA dot blots to examine tissue specificity and by Northern blots to examine the transcript size of the corresponding mRNA. The computer analysis identified 15 promising genes that were previously unidentified. When seven of these were examined in an RNA hybridization experiment, three were found to be prostate specific. The genes identified could be useful in the targeted therapy of prostate cancer. The procedure can easily be applied to discover genes specifically expressed in other organs or tumors.
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PMID:Discovery of three genes specifically expressed in human prostate by expressed sequence tag database analysis. 941 70

Tumor cell-specific homozygous deletions coinciding at a particular genetic location may indicate the inactivation of a nearby tumor suppressor gene. Forty-six human cancer cell lines of prostate, pancreatic, lung, liver, and colon origin were screened for homozygous deletions of 139 expressed sequence tag (EST) and sequence-tagged site (STS) loci spanning the entire short arm of chromosome 8. Only one Southern blot-verified homozygous deletion was detected in this set of cell lines. The deletion, in pancreatic tumor cell line MIA-PaCa-2, encompassed two screening loci, D8S549 and D8S1992, and overlapped another previously described homozygous deletion of band 8p22 in a metastatic prostate cancer specimen. Both deletions entirely removed the candidate tumor suppressor gene N33. These data define a consensus homozygous deletion region in chromosome band 8p22.
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PMID:High-density screen of human tumor cell lines for homozygous deletions of loci on chromosome arm 8p. 989 7

The identification of homozygous deletions in malignant tissue is a powerful tool for the localization of tumor suppressor genes. Representational difference analysis (RDA) uses selective hybridization and the polymerase chain reaction (PCR) to isolate regions of chromosomal loss and has facilitated the identification of tumor suppressor genes, such as BRCA2 and PTEN. We have recently identified a 1-5-cM homozygous deletion on 12p12-13 in a prostate cancer xenograft and found that 47% of patients who died of prostate carcinoma demonstrate focal loss of heterozygosity (LOH) in this region in metastatic deposits. We have now characterized the region of interest by assembling a yeast artificial chromosome (YAC) contig spanning the homozygous deletion and identifying which known genes and expressed sequence tags (EST) lie within the homozygous deletion. A rib metastasis was harvested at autopsy and placed subcutaneously in a male SCID mouse. Genomic DNA from this xenograft and from the patient's normal renal tissue was extracted. Multiplex PCR, with the xenograft and normal DNA used as template, was performed using primers for loci on the Whitehead contig 12.1 believed to be near our region of interest. We found that our deletion lay in a 1-2-Mb interval between WI-664 and D12S358. We then used the same primers to construct a YAC contig across the homozygous deletion. PCR amplification of YAC DNA, using primers for the genomic sequences of known genes and ESTs reported to lie on 12p12-13, was used to identify candidate genes that lay within the deletion. Duplex PCR, with control primers known not to be deleted in the xenograft, was used to confirm that both the CDKN1B and ETV6 genes were homozygously deleted in the xenograft. Mutations in either or both of these genes may play an important role in metastatic prostate carcinoma.
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PMID:Deletion mapping at 12p12-13 in metastatic prostate cancer. 1037 73

In a search for prostate-specific genes in the human expressed sequence tag (EST) database, we identified a seemingly unique EST cluster C81. Experimental data linked C81 to the human hKLK2 gene that encodes a prostate specific serine protease-human glandular kallikrein (hK2). We uncovered a full-length hKLK2 cDNA corresponding to a 3.0 kb hKLK2 mRNA by PCR and sequence analysis. The 3.0 kb transcript accounts for about 25% of the hKLK2 transcripts as compared to the previously known 1.5 kb transcript. We also identified a third spliced form of the hKLK2 gene produced by alternative splicing between intron III and exon 4. This spliced form was detected in normal prostate, prostate cancer and the prostate adenocarcinoma cell line LNCaP. The identification of long hKLK2 transcript and an alternative spliced form of the hKLK2 gene indicates that regulation of the gene is complex.
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PMID:Identification of three new alternate human kallikrein 2 transcripts: evidence of long transcript and alternative splicing. 1054 17

The expressed sequence tag (EST) databases are an attractive starting point for gene discovery for diseases like cancer. Validation of gene targets from these sequences (both known and novel) in cancers requires a comprehensive expression profiling. We identified from the Cancer Gene Anatomy Project database (CGAP), a hit called neurotensin receptor (NT-r) that was expressed in the pancreatic cancer cDNA libraries. Neurotensin (NT), a neuroendocrine peptide, exerts trophic effects in vivo and stimulates the growth of cancer-derived cell lines in vitro. High affinity neurotensin receptors (NT-r) are expressed in cancer-derived cell lines and in some primary tumors. To date, a comprehensive expression profile of the NT-r in diverse cancers and normal tissues has not been reported. A cancer-selective expression of NT-r, if demonstrable, may provide a basis for a diagnostic and potential therapeutic utility. We demonstrate that the NT-r is expressed in a variety of cancer-derived cell lines as well as primary tumors, but only in a select few normal tissues. The expression of NT, on the other hand, was detected in many normal tissues, but not in the cancer-derived cell lines. The NT expression however, was detected in the primary tumors. We further demonstrate that NT expression is stimulated by androgen deprivation in the prostate cancer models. These results demonstrate the usefulness of a panel of cDNA repository for rapid validation of potential cancer targets.
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PMID:Relevant genomics of neurotensin receptor in cancer. 1076 34

Prostate cancer tends to become transformed to androgen-independent disease over time when treated by androgen-deprivation therapy. We used two variants of the human prostate cancer cell line LNCaP to study gene expression differences during prostate cancer progression to androgen-independent disease. Production of prostate-specific antigen was regarded as a marker of androgen-dependence and loss of prostate-specific antigen was regarded as a marker of androgen-independence. mRNA from both cell lines was used for cDNA microarray screening. Differential expression of several genes was confirmed by Northern blotting. Monoamine oxidase A, an Expressed Sequence Tag (EST) similar to rat P044, and EST AA412049 were highly overexpressed in androgen-dependent LNCaP cells. Tissue-type plasminogen activator, interferon-inducible protein p78 (MxB), an EST similar to galectin-1, follistatin, fatty acid-binding protein 5, EST AA609749, annexin I, the interferon-inducible gene 1-8U, and phospholipase D1 were highly overexpressed in androgen-independent LNCaP cells. All studied genes had low or no expression in PC-3 cells. The EST similar to rat P044, the EST similar to galectin-1, follistatin, annexin I, and the interferon-inducible gene 1-8U were also expressed in benign prostatic hyperplasia tissue. The Y-linked ribosomal protein S4, Mat-8, and EST AA307912 were highly expressed in benign prostatic hyperplasia tissue. Additionally, both confirmation of differential expression in Northern blots and in situ hybridization were carried out for monoamine oxidase A, the EST similar to rat P044, the EST similar to galectin-1, fatty acid-binding protein 5, and the interferon-inducible gene 1-8U. We identified several potential prostate cancer markers, indicating that the method used is a useful tool for the screening of cancer markers, but other methods, such as in situ hybridization, are needed to further investigate the observations.
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PMID:Differentially expressed genes in two LNCaP prostate cancer cell lines reflecting changes during prostate cancer progression. 1095 Jan 17

The molecular mechanisms underlying the development and progression of prostate cancer have remained poorly understood. The identification of differentially expressed genes has been used as a tool to recognize genes that are involved in disease processes. In this study we combined suppression subtractive hybridization (SSH) and cDNA array hybridization to identify genes whose expression is decreased in prostate cancer. cDNA from benign prostatic hyperplasia (BPH) was subtracted with cDNA from the prostate cancer cell line PC-3 and 386 of the subtracted clones were arrayed onto a nylon filter membrane. The differential gene expression was then verified by hybridizing the filter with radioactively labelled first-strand cDNA preparations from BPH, PC-3, four other cancer cell lines, and a normal prostate epithelial cell line (PrEC). In order to validate SSH and cDNA array hybridization, the enrichment of clones in the subtraction, as well as the sensitivity and linearity of array hybridization, was first evaluated. The array hydridization results were confirmed by northern analysis and selected clones were sequenced. Altogether, several known genes, such as prostate-specific antigen (PSA), human glandular kallikrein 2 (hK2), phosphatidic acid phosphatase type 2a (PAP2a), alpha-tropomyosin, and insulin-like growth factor binding protein 7 (IGFBP-7), as well as an anonymous transcript (EST), were found to be expressed less in PC-3 than in BPH. Further studies on the significance of these genes in the development of prostate cancer are now warranted.
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PMID:Detection of differentially expressed genes in prostate cancer by combining suppression subtractive hybridization and cDNA library array. 1116 18

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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PMID:Gene expression analysis of prostate cancers. 1180 55

Differentially expressed genes between corresponding normal and cancertissue can advance our understanding of the molecular basis of malignancy and potentially serve as biomarkers or prognostic markers of malignancy. To identify differentially expressed genes in prostate cancer, we used a procedure combining electronic expression profiling of the prostate expressed sequence tag (EST) database and molecular biology techniques. A novel electronic expression-profiling algorithm was developed to search publicly available EST sequences for genes that show significant differential expression in prostate cancer compared with normal prostate tissue. Approximately 600 genes expressed in prostate were identified through adequate EST counts of ESTs for electronic profiling. Of these 600 genes, 9 showed statistically significant differences in their EST counts between cancer and normal prostate and were further analyzed. The predictions associated with electronic profiling were experimentally verified for two genes, cysteine-rich secretory protein 3 (CRISP-3) and deadenylating nuclease (DAN), using real-time reverse transcription-PCR with total RNA extracted from cells isolated by laser capture microdissection. In five of five Gleason score 6 cancer cases, CRISP-3 expression was increased >50 fold, whereas the expression of DAN was reduced by >80%.
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PMID:Identification of differentially expressed genes in normal and malignant prostate by electronic profiling of expressed sequence tags. 1203 49

To understand the phenotypic changes associated with prostate cancer development and metastasis, we investigated differential gene expression in primary and established prostate cell lines used as models. We have used a differential display of messenger RNA (DDRT-PCR) technique using 168 primer combinations and total RNA from BPH-1, LNCaP, and PC3 cells to identify filter-based cDNA microarrays containing 18,376 nonredundant clones of genes and expressed sequence tags (EST) using mRNA from PrEC and MDAPCa2a cells to identify genes that are differentially expressed in normal, benign, and cancerous prostate cell lines. Twenty-five cDNA with a significant difference in expression of 76 candidate cDNA, as identified by DDRT-PCR and confirmed by slot-blot analysis, were selected for sequence analysis. Of these, 14 cDNA were further confirmed by Northern blot analysis. Analysis of the cDNA microarray data showed that a variety of genes/EST were up- or down-regulated in the metastatic prostate tumor cells and a majority of these genes encode cytoskeletal proteins and proteins with regulatory function. Expression profile of two EST was confirmed by reverse transcription polymerase chain reaction. We also have identified a number of genes exhibiting differential expression in prostate cancer cells, which were not known earlier to be involved in prostate cancer. This report provides a comparative analysis of differential gene expression between normal prostatic epithelial cells and prostate cancer cells, and a foundation to facilitate in-depth studies on the mechanism of prostate cancer development and metastasis.
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PMID:Profiling of differential expression of messenger RNA in normal, benign, and metastatic prostate cell lines. 1255 Jul 71


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