Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

When a non-metastatic subline from the Dunning rat prostatic cancer was transfected with the v-Ha-ras oncogene, some transfectants acquired metastatic potential. Molecular analysis demonstrated that there was no simple dose-response relationship between v-Ha-ras expression and metastatic potential in this prostatic cancer system. Cytogenetic analysis on the same system demonstrated increased genetic instability following v-Ha-ras transfection. Progression of prostatic cancer from no metastatic to high metastatic potential may involve the loss of a metastasis suppressor gene. To test this possibility, non-metastatic and highly metastatic Dunning rat prostatic cancer cells were fused. Hybrid clones were isolated that conserved the chromosomes from their parental cells. When these hybrids were injected into animals, none developed distant metastases. When the non-metastatic primary tumours were passaged in vivo, distant metastases developed in occasional animals. Cytogenetic analysis of eight of these metastatic revertants demonstrated a consistent loss of normal chromosome 2. These studies show that metastasis is associated with the loss of a specific chromosome. These studies also suggest that a metastasis suppressor gene for rat prostatic cancer is located on chromosome 2. A more direct approach to identify a chromosome(s) carrying metastasis suppressor gene(s) by using microcell mediated chromosome transfer is currently progressing.
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PMID:Genetic factors and metastatic potential of prostatic cancer. 184 56

Progression of prostatic cancer from nonmetastatic to high metastatic ability may involve the loss of a metastasis suppressor gene. To test this possibility, nonmetastatic and highly metastatic Dunning rat prostatic cancer cells were fused. Hybrid clones were isolated which conserved the chromosomes from their parental cells. When these hybrids were injected into animals, none developed distant metastases. When these nonmetastatic primary tumors were passaged in vivo, occasional animals developed distant metastases. Cytogenetic analysis of eight of these metastatic revertants demonstrated a consistent loss of a copy of a normal chromosome 2. Although previous studies have demonstrated that specific chromosomes can inhibit tumorigenicity in cell fusion experiments, this is the first study to show that prostatic cancer metastasis is associated with the loss of a specific chromosome. Furthermore, these studies suggest that a metastasis suppressor gene for rat prostatic cancer is located on chromosome 2.
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PMID:Genetic factors and suppression of metastatic ability of prostatic cancer. 206 33

Metastasis suppressor activities have previously been mapped to human chromosomes 17 and 11. Decreased expression of the metastasis suppressor gene NM23, which is located on chromosome 17, has been correlated with increased metastatic potential in mammary cancers. A region on human chromosome 11, from 11p11.2-p13, has been shown to suppress metastasis in rat prostatic carcinoma cells. In both cases the metastasis suppressor activity had no effect on tumorigenicity or tumor growth rate, demonstrating that the encoded activities are distinct from effects of tumor suppression. To determine whether these human chromosomes encode general or tissue-specific metastasis suppressor activities, a truncated human chromosome 17 (i.e., pter-q23) and a full-length human chromosome 11 were separately transferred into highly metastatic rat mammary and prostate cancer cell lines and tested for their ability to suppress spontaneous metastasis in vivo. These studies demonstrated that when the pter-q23 region of human chromosome 17 is retained by the microcell hybrids, the metastatic ability of both mammary and prostatic cancer cells is suppressed. In contrast, when the pter-q14 region of human chromosome 11 is retained, only the metastatic ability of prostatic cancer cells is suppressed. Additional studies demonstrated that the metastasis suppressor activity encoded by the chromosome 17 pter-q23 region is p53-independent and not due to enhanced expression of NM23 protein.
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PMID:Differential suppression of mammary and prostate cancer metastasis by human chromosomes 17 and 11. 795 74

In previous allelotype analyses of human prostatic cancer specimens, allelic loss on the short arm of chromosome 8 is frequently observed. However, it is still unclear whether this allelic loss is an initial event or a later one in development of prostatic cancer. Our previous studies demonstrate that introduction of human chromosome 11 into highly metastatic rat prostatic cancer cells results in suppression of metastatic ability without suppression of the in vivo growth rate or tumorigenicity of the hybrid cells (T. Ichikawa et al. Cancer Res., 52: 3486-3490, 1992). To clarify the role of human chromosome 8 in prostatic cancer, this chromosome was introduced into highly metastatic rat prostatic cancer cells using microcell-mediated chromosome transfer. Introduction of human chromosome 8 resulted in suppression of metastatic ability of the microcell hybrids, whereas no suppression of the in vivo growth rate or tumorigenicity was observed. These results demonstrate that human chromosome 8 contains metastasis suppressor gene(s) for prostatic cancer derived from a rat. These also suggest that human chromosome 8 has an important role in development of prostatic cancer.
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PMID:Suppression of metastasis of rat prostatic cancer by introducing human chromosome 8. 816 68

To examine the role of human chromosome 10 in development of prostatic cancer, we introduced human chromosome 10 into highly metastatic rat prostatic cancer cells by microcell-mediated chromosome transfer. Microcell hybrid cells introduced with human chromosome 10 showed suppression of the metastatic ability to the lung to some extent without any suppression of tumorigenicity, although the tumor growth rate decreased slightly. To minimize the region that contains metastasis suppressive activity, the hybrid cells in metastasis foci of lung were established in culture and reanalyzed for portions of human chromosome 10 retained in the metastasis tissues. Cytogenetic and molecular analyses demonstrated that loss of the region between 10cen and D10S215 on human chromosome arm 10q was related to expression of the metastatic phenotype. These results demonstrate that the region between 10cen and D10S215 on human chromosome arm 10q contains at least one of the metastasis suppressor genes for rat prostatic cancer.
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PMID:Localization of metastasis suppressor gene(s) for rat prostatic cancer to the long arm of human chromosome 10. 852 92

To examine the role of human chromosomes in the development of metastatic prostate cancer, we introduced a copy of human chromosomes into highly metastatic Dunning R-3327 rat prostatic cancer cells by microcell-mediated chromosome transfer. Each microcell hybrid clones containing human chromosomes 8, 10, 11, and 17, respectively, showed decreased ability to metastasize to the lung, without any loss of tumorigenicity. This finding demonstrates that these human chromosomes contain metastasis suppressor genes for prostate cancer. Spontaneous deletion of portions of human chromosomes was observed in human chromosome 10, 11, and 17 studies. In the human chromosome 8 study, irradiated microcell-mediated chromosome transfer was performed to enrich chromosomal arm deletions of human chromosome 8. Relationships between the size of human chromosomes introduced into microcell hybrid clones and the number of lung metastases produced by the clones were analyzed to determine which part of human chromosomes contained metastasis suppressor gene(s) for prostate cancer. Molecular and cytogenetic analyses of microcell hybrid clones demonstrated that metastasis suppressor genes on human chromosomes 8, 10, and 11 were located on 8p23-q12, 10q, 11p13-11.2, respectively. Further analyses are proposed to confirm the potentially useful advantage of this assay system to identify metastasis suppressor gene(s) for prostate cancer.
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PMID:Metastasis suppressor genes for prostate cancer. 863 Feb 27

KAI1 is a metastasis suppressor gene for prostate cancer that is located on chromosome 11p11.2-13. Using Northern blot analysis and in situ hybridization, we studied expression of KAI1 mRNA in specimens from 14 normal pancreases and 27 primary pancreatic cancers, and then correlated the findings with the clinical and histopathological parameters of the patients. Northern blot analysis showed increased steady-state levels of KAI1 mRNA expression in 24 of 27 (89%) pancreatic cancer samples. In situ hybridization showed enhanced KAI1 mRNA levels in the pancreatic cancer cells in 82% cancer tissues. The stroma surrounding the cancer mass and normal pancreatic tissue adjacent to the cancer cells exhibited very low levels of KAI1 mRNA expression. Correlation of the mRNA levels obtained by Northern blot analysis with clinical parameters of the patients revealed that KAI1 mRNA levels were significantly higher (P < 0.01) in earlier tumor stages (I, II), compared with advanced tumor stages (III, IV) in which lymph node or distant metastases were present. Furthermore, poorly differentiated tumors had significantly higher KAI1 mRNA levels than those that were moderately or well differentiated (P < 0.05). No association between KAI1 expression and survival was found. Our results indicate that KAI1 mRNA expression is reduced in patients with advanced tumor stages. This suggests that reduction of KAI1 expression might enable pancreatic cancer cells to spread in lymph nodes and to distant organs.
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PMID:KAI1 expression is up-regulated in early pancreatic cancer and decreased in the presence of metastases. 889 37

Our previous studies demonstrated that human chromosome 8 contains metastasis suppressor gene(s) for rat prostate cancer. However, it is still unknown which portion of human chromosome 8 is associated with suppression of metastatic ability, because all of the clones in which metastatic ability is suppressed contain at least one copy of intact human chromosome 8. In the present study, we used the irradiated microcell-mediated chromosome transfer technique to enrich for specific chromosomal arm deletions of selected chromosomes. The resultant series of human chromosomes 8 with a variety of chromosomal deletions was introduced into highly metastatic Dunning rat prostate cancer cells. All of the resultant microcell hybrids showed reduced metastatic ability. To obtain a smaller size of human chromosome 8 and to locate further the region of metastasis suppressor gene(s), the most reduced size of human chromosome 8 that was generated with the initial irradiated chromosome transfer was retransferred into the Dunning cancer cells without irradiation. The resultant microcell hybrids were analyzed to determine which portion of human chromosome 8 suppressed the metastatic ability of the recipient cells. This analysis demonstrates that the portion of human chromosome 8 containing metastasis suppressor gene(s) for rat prostate cancer cells lies on human chromosome segment 8p21-p12, where frequent allelic losses have been detected in allelotype analyses of human prostate cancer. This suggests that one of the metastasis suppressor genes for rat prostate cancer on human chromosome 8 may also play an important role in the progression of human prostate cancer.
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PMID:Mapping of metastasis suppressor gene(s) for rat prostate cancer on the short arm of human chromosome 8 by irradiated microcell-mediated chromosome transfer. 894 8

We have used microcell fusion-mediated chromosomal transfer to introduce normal human chromosomes into highly metastatic rodent prostatic cancer cells to map the location of a metastasis suppressor gene(s). Using this approach, several chromosomal regions have been identified that harbor such metastatic suppressor genes, including human chromosome 11 between p11.2-13 (T. Ichikawa et al., Cancer Res., 52: 3486-3490, 1992, 54: 2299-2302, 1994; N. Nihei et al., Genes Chromosomes & Cancer, 14: 112-119, 1995; C. W. Rinker-Schaeffer et al., Cancer Res., 54: 6249-6256, 1994). Using positional cloning, a metastatic suppressor gene, termed KAI1, was identified, which is located at human chromosome 11p11.2 (5). Overexpression of KAI1 results in metastasis suppression in certain highly metastatic Dunning R-3327 rat prostatic cancer sublines, such as AT6.1, without metastasis suppression in other highly metastatic sublines, such as AT3.1. This suggests that an additional metastasis suppressor gene is located within the human chromosome 11p11.2-13 region. The CD44 gene is located on human chromosome 11p13 and encodes an integral membrane glycoprotein that participates in specific cell-cell and cell-extracellular matrix interactions. Down-regulation of CD44 expression both at the mRNA and protein levels correlates with metastatic potential within the Dunning system of rat prostatic cancer sublines. Transfection-induced enhanced expression of the Mr 85,000 standard form of CD44 in the highly metastatic AT3.1 rat prostatic cells greatly suppresses their metastatic ability to the lungs without suppression of their in vivo growth rate or tumorigenicity. These results suggest that CD44 is a metastasis suppressor for prostatic cancer and that decreased expression of the standard form of CD44 is involved in the progression of prostatic cancer to a metastatic state.
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PMID:CD44 is a metastasis suppressor gene for prostatic cancer located on human chromosome 11p13. 904 Nov 84

Prostate cancers account for 43% of all cancers diagnosed in American men. It is estimated that in 1996, 317,000 new cases of prostate cancer were diagnosed and 41,000 men died of the disease. The challenge of treating prostate cancer lies in accurately distinguishing those histologically-localized cancers which will complete metastatic progression from those that will remain indolent. At this time, we lack appropriate histological markers to make such distinctions, therefore, it is often difficult to accurately predict the clinical course of an individual patient's disease. There is growing evidence that a critical event in the progression of a tumor cell from a non-metastatic to metastatic phenotype is the loss of function of metastasis-suppressor genes. These genes specifically suppress the ability of a cell to metastasize. Work from several groups has demonstrated that human chromosomes 8, 10, 11 and 17 encode prostate cancer metastasis suppressor activities. As a result of these efforts the first prostate cancer metastasis-suppressor gene, KAI1, was identified and mapped to the p11-2 region of chromosome 11. In subsequent studies, an additional gene encoded by the same region, CD44 was also determined to have metastasis-suppressor activity. Recent studies have shown a correlation between decreased expression of KAI1 and CD44 and an increased malignant potential of prostate cancers. It is anticipated that the identification of other metastasis suppressor genes may allow for the development of diagnostic markers useful in the clinical substaging of individual tumors. This manuscript is intended to present our perspective on the importance of these genes in the understanding of prostate cancer progression. More importantly, we present new findings from our laboratory's effort to identify the metastasis-suppressor genes encoded by human chromosome 17. Specifically we report the strategy currently being used to evaluate a series of candidate genes and the approach being utilized to pinpoint the metastasis-suppressor region on human chromosome 17.
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PMID:Prostate cancer metastasis-suppressor genes: a current perspective. 957 26


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