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Query: UMLS:C1326912 (tumorigenesis)
 57,481 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In studies on the onset and progression of cancer, molecular biology has proven to be very useful. Reasoning that tumorigenesis can be considered as a multistep process in which a normal cell gradually escapes from its delicately regulated growth pattern, one might describe this process in terms of gene expression. The group of genes that are good candidates for such studies are the proto-oncogenes. Recent progress in oncogene research, however, has made us believe that the group of oncogenes is much greater than the 50 so far characterized, since all growth factor-, growth factor receptor-, signal transducer- and transcription-regulating genes have a potency to become oncogenic. Alternatively, recessive genes, such as tumor suppressor genes, might be equally relevant to the onset and progression of cancer. Therefore, new approaches in molecular studies on the genesis and progression of malignancies are urgently needed. One of these methods is the so-called differential or subtraction hybridization analysis. Particularly, the rationale of differential hybridization and the first applications to prostate cancer research are discussed in this paper.
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PMID:Identification of new prostate cancer progression markers by differential hybridization analysis. 142 40

Structural variants of nuclear hormone receptors have been found in tumour tissues. Experimental evidence suggests two ways in which these variants may have oncogenic potential: 1. by suppressing the action of the normal hormone receptor, thereby acting as dominant negative oncogenes; 2. by activating hormone-responsive genes in a hormone-independent manner. These mechanisms may not only contribute to oncogenesis but also to the development of hormone resistance in tumours, e.g. breast and prostate cancer.
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PMID:Nuclear hormone receptor variants: their role in malignancy and progression to hormone resistance in cancer. 166 42

Advances in molecular genetic techniques have reached the point where clinical material can be reasonably well-characterized in detail. One area that is receiving increasing attention is the genetic abnormalities of tumors. Using the technique of restriction fragment length polymorphism analysis, it is possible today to build up a picture of the genome and to identify which regions are deleted or are rearranged in the tumor cells of an individual patient. Twenty years ago, experimental and theoretical findings suggested that loss of gene function could be an essential component in oncogenesis. Such genes have been named tumor suppressor genes. The significance of the consistent loss of specific regions of genetic information from the genomes of tumor cells of a particular histological type is now appreciated, as such areas may contain as yet unrecognized tumor suppressor genes. The characterization of regions consistently lost thus forms the first step in localizing such genes. We have applied this technology to the study of prostate cancer and our preliminary findings show consistent losses of genetic information from chromosomes 8, 10, and 16.
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PMID:Molecular genetics and human prostatic carcinoma. 167 4

A detailed deletion mapping of a series of human prostatic carcinomas, using restriction fragment length polymorphism (RFLP) analysis of all chromosomes, showed allelic losses on individual chromosomes at variable frequencies. Allelic losses occurred on chromosomal arms 8p, 10pq, 16q and 18q in more than 30% of the cases. Losses of genetic information from one or two of the chromosomes 8, 10, or 16 were always present in tumors showing allelic losses, indicating that genes on these chromosomes have a central role in prostatic cancer. A more extensive study of these chromosomes was thus carried out and showed the highest frequency of allelic deletions to occur on the short arm of chromosome 8 (65%) (where the minimally deleted region was between the PLAT locus and pter). The long arm of chromosome 16 had allelic deletions in 56% of informative cases, with three different break points (the most distal being between D16S4 and D16S7). Chromosome 10 exhibited a complex deletion pattern, showing allelic losses from both the short (p) and the long (q) arms, evidence of non-reciprocal translocations of the q arm, and monosomy in some cases. Our data indicate that tumor suppressor genes involved in the oncogenesis of prostatic carcinoma may be localized between 8pter and the PLAT locus and that additional/alternative tumor suppressor gamma are likely to be localized on chromosome 10 and on the long arm of chromosome 16. More aggressive tumors were accompanied by a high or frequency of allelic losses.
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PMID:Recessive genetic mechanisms in the oncogenesis of prostatic carcinoma. 168 23

Tumor growth and metastasis are angiogenesis-dependent. Virtually all solid tumors are neovascularized by the time they are detected. However, there is a prevascular phase during early tumor development where few or no tumor cells are angiogenic and expansion of the tumor is restricted to a few mm3. When enough tumor cells become angiogenic, the tumor can expand progressively and shed metastatic cells. This angiogenic switch has recently been quantitated for human breast cancer, as well as for prostate cancer. We have studied the problem of how tumors switch to the angiogenic phenotype by using transgenic mice in which tumors develop at a predictable time and in discrete prevascular and vascular stages. When the transgene is the bovine papilloma virus (BPV) genome, angiogenic fibrosarcomas develop from non-angiogenic precursors called fibromatoses. The fibrosarcomas secrete growth factors for capillary endothelial cells. In contrast, the fibromatoses do not secrete endothelial cell growth factors. When the transgene consists of the large "T" antigen of SV40 under the control of the rat insulin promoter, 70% of pancreatic islets become hyperplastic and 4-10% of these become angiogenic at 6-7 weeks. Tumors arise from these neovascularized hyperplastic islets and reach > 1000 x the volume of the preangiogenic islets. The onset of angiogenic activity coincides with the secretion of acidic fibroblast growth factor (aFGF) and other growth factors not fully identified at this writing. These studies help to explain the switch to the angiogenic phenotype during tumorigenesis and provide models to discover antiangiogenic therapies directed at the source of angiogenic activity. Such therapy, when developed, may be co-administered with currently available angiogenesis inhibitors which are directed at the target of angiogenic activity, vascular endothelial cells.
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PMID:Switch to the angiogenic phenotype during tumorigenesis. 172 33

Evidence supporting a broad role for the inactivation of the p53 gene in human tumorigenesis has been provided by studies showing that the p53 gene is mutated in many human cancers. In this study, we report on the mutational status of the p53 gene in prostate cancer cells and provide functional evidence that the wild-type p53 gene may have a role in suppressing prostatic tumorigenesis. Sequence analysis of exons 5-8 of the p53 gene reveals that three of five prostate cancer cell lines (TSUPr-1, PC3, DU145) contain mutations which alter the amino acid sequence of this most highly conserved portion of the gene. One of two primary prostatic cancer specimens examined also contained a mutation in this region. Transfection of the wild-type p53 gene versus a mutated p53 gene into two cell lines with p53 mutations results in reduced colony formation. Wild-type p53 gene expression is apparently incompatible with continued growth of these tumor cells inasmuch as none of the colonies which formed after wild-type transfections retain the transfected p53 sequences. Immunocytochemical data indicate that prostate carcinoma cells expressing the transfected wild-type p53 gene are growth arrested because they exhibit a reduced level of thymidine incorporation into DNA. This study is the first report of p53 gene mutations in prostate cancer cells and suggests a functional role for the p53 gene in suppressing prostatic tumorigenesis.
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PMID:Wild-type p53 suppresses growth of human prostate cancer cells containing mutant p53 alleles. 187 16

Molecular biology has proven to be instrumental in studies on the onset and progression of cancer. Reasoning that tumorigenesis can be considered as a multistep process in which a normal cell gradually escapes from its delicately regulated growth pattern, one might describe this process in terms of gene expression. The group of genes that are good candidates for investigation in this context are the proto-oncogenes. Recent progress in oncogene research, has led us to believe that the group of oncogenes is much greater in number than the fifty so far characterized, since all growth factor-, growth factor receptor-, signal transducer- and transcription regulating genes have a potency to become oncogenic. Recessive genes, such as tumor suppressor genes might be equally relevant to the onset and progression of cancer. In this paper we confine ourselves to the role of protooncogenes in urological cancers, in particular prostate cancer. The usefulness of these genes as markers of progression in prostate cancer will be discussed.
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PMID:Oncogene expression in prostate cancer. 221 84

Accumulation of mutations in oncogenes and tumor suppressor genes transforms a normal cell into a malignant cell by allowing it to escape from normal control of growth. In prostate tumorigenesis, the current model envisages specific mutations of the TP53 tumor suppressor gene and loss of loci, detected by loss of heterozygosity (LOH), on chromosome arms 8p, 10q, 16q, and 18q. In order to determine if alterations frequently found in other adenocarcinomas (breast, ovarian, gastric, colorectal), including losses of genetic material from chromosome arms 1p, 3p, 7q, 8p, 11p, 17p, 17q, and 18q, are also involved in prostate cancer, we examined 20 localized early-stage prostate tumors. We detected no mutations of the TP53 gene. Allelic losses were found from 7q (33%), 8p (50%), 10q (20%), and 18q (33%). Furthermore, as the first step toward isolating tumor suppressor genes on 18q, we used six polymorphic markers and identified a small common deleted region between the chromosome 18 centromere and the D18S19 locus.
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PMID:Genetic alterations in localized prostate cancer: identification of a common region of deletion on chromosome arm 18q. 752 48

CD44 is a glycosylated adhesion molecule which may undergo alternative splicing of 10 possible exons to generate variant isoforms. A number of CD44 variant isoforms expressed by tumor cells have been correlated with metastatic and proliferative behavior. In this study, we have characterized CD44 isoform expression on three prostate cancer cell lines: ALVA-31, PPC-1, and LNCaP. Using reverse transcriptase-polymerase chain reaction, we have found that ALVA-31 and PPC-1 cells express multiple CD44 isoforms, including CD44s (standard form), CD44E (epithelial form), and an exon 14-containing form. In addition, two smaller forms have been detected: one using an alternative donor splice site within exon 5, and a novel form omitting exon 5 entirely. The CD44 isoforms expressed by ALVA-31 and PPC-1 cells appear to be preferentially located on the cell surface. By contrast, LNCaP cells do not express any of the CD44 forms at the RNA or protein level. Both PPC-1 and ALVA-31 cells display tumorigenesis and invasiveness in nude mice, whereas LNCap cells exhibit a less malignant phenotype, suggesting a correlation between CD44 variant (CD44v) expression and aggressive prostate tumor behavior. Functional characterization reveals that CD44 mediates prostate cell adhesion to extracellular hyaluronic acid (HA). In addition, the CD44 cytoplasmic domain binds specifically to ankyrin, a membrane cytoskeletal protein. Double immunofluorescence labeling and confocal microscopic analyses indicate that HA binding induces the HA receptor (i.e., CD44) to form capped structures. Importantly, intracellular ankyrin is preferentially accumulated underneath HA receptor-capped structures. These results suggest that cytoskeletal proteins such as ankyrin are closely associated with CD44-mediated signaling events induced by HA. Finally, HA-mediated transmembrane interactions between CD44 isoforms and cytoskeletal proteins (i.e. ankyrin) may play a pivotal role in regulating tumor cell behavior during human prostate cancer development.
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PMID:Interaction of CD44 variant isoforms with hyaluronic acid and the cytoskeleton in human prostate cancer cells. 754 57

The necessity of early detection of prostate cancer renewed interest regarding putative premalignant lesions in the tumorigenesis of the prostate. Prostatic intraepithelial neoplasia (PIN) is one potential precursor for prostatic adenocarcinoma. The term PIN has been adopted to replace a wide range of synonyms in the literature that describe potential precursors. PIN is an intraluminal proliferation of the secretory cells lining architecturally benign prostatic ducts and acini that exhibit cytologic atypia. In this review, we discuss the histologic features, the differential diagnosis, the evidence that PIN is a precursor of prostatic carcinoma, and the clinical significance of PIN.
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PMID:Prostatic intraepithelial neoplasia: a potential precursor lesion of prostatic adenocarcinoma. 766 Jun 73


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