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)

As part of our evaluation of members of the transmembrane 4 super-family as possible prognostic predictors, we performed a retrospective study on the expression of the recently identified KAI1 gene by tumors of the lung. This gene, which is identical to CD82, suppresses tumor metastasis of prostate cancer, and its decreased expression may be involved in malignant progression. We used reverse transcription-PCR to analyze tumor tissues from 151 lung cancer patients; 74 tumors were stage I, 17 were stage II, and 60 were stage III. Our results indicate that while 35 patients had tumors in which the KAI1/CD82 gene was conserved (positive), 116 patients had tumors with reduced gene expression (negative). The overall survival rate of patients with KAI1/CD82-positive tumors was significantly higher than that of patients with KAI1/CD82-negative tumors (77.4% versus 38.5%; P=0.002). Furthermore, the overall survival rate of patients with KAI1/CD82-positive adenocarcinoma was also much higher than that of individuals whose adenocarcinoma had reduced KAI1/CD82 expression (73.4% versus 27.1%;P=0.009). Multivariate analysis with the Cox regression model indicated that KAII/CD82 positivity correlated best with the overall survival rate, except for lymph node status. Our data suggest that high KAII/CD82 gene expression by tumors of the lung may be associated with a good prognosis. These findings complement our earlier studies on MRP-1/CD9, another member of the transmembrane 4 superfamily, whose reduced expression in non-small cell lung cancer appears to be a factor of poor prognosis. This set of observations suggests that assessment of the expression status of KAI1/CD82 and MRP-1/CD9 by tumors may provide prognostic information on the clinical behavior of lung cancer.
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PMID:Correlation of KAI1/CD82 gene expression with good prognosis in patients with non-small cell lung cancer. 862 Apr 88

The KAI1 gene, recently identified as a metastatic suppressor gene for prostate cancer, was cloned and was revealed to be identical to the C33/IA4/ R2/4R9 gene. The expression of KAI1 protein was examined immunohistochemically in the tissues from 14 cases of benign prostatic hyperplasia and 46 cases of prostate cancer using mouse monoclonal anti-human C33 antibody. In benign prostatic hyperplasia tissues, KAI1 protein was uniformly expressed in the glandular cell membrane at cell-to-cell borders. The KAI1 protein in the tissues of untreated prostate cancer was also located at similar sites to those of benign prostatic hyperplasia, but the percentage of strongly positive cancer cells was correlated inversely to the Gleason pattern (P < 0.0001, one-way analysis of variance). There was also a statistically inverse correlation between the percentage of KAI1-positive cancer cells and the clinical stage (chi 2 = 9.6; P = 0.0081). In 4 cancer death cases relapsed from endocrine therapy, KAI1 protein was not stained in either primary or metastatic foci. These results indicate that the expression of KAI1 protein correlates to tumor characteristics in prostate cancer.
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PMID:Expression of the KAI1 protein in benign prostatic hyperplasia and prostate cancer. 890 32

The transmembrane 4 superfamily member KAI1 (CD82) has been shown to inhibit pulmonary metastases in experimental metastasis models of prostate cancer and melanoma. KAI1 expression is decreased in the progression of common solid epithelial tumors of adulthood, including lung, prostate, breast, esophageal, gastric, pancreatic, and bladder cancers. The purpose of our study was to investigate KAI1 expression in the progression of human colorectal cancer. We first analyzed 20 colorectal cancer cell lines by immunoblot techniques. KAI1 was expressed heterogeneously, with the tumor cell lines having a more complex degree of glycosylation compared with that of the normal colonic tissue. KAI1 was highly expressed in the primary SW480 colon cancer cell line but was down-regulated 15-fold in the matched metastatic SW620 cell line. We also investigated KAI1 protein expression by immunohistochemistry in tissues from 84 patients with colorectal cancer. Each tissue section was assigned a KAI1 mean score (KMS) from 0 to 300 based on the product of the percentage of cells that stained for KAI1 and the intensity of the stain (1, 2, or 3). In 84 patients with colorectal cancer, KAI1 was expressed at high levels in normal colonic mucosa (KMS 226) but was expressed at lower levels in the primary tumors (KMS 65; P < 0.0001). In a subset of 12 patients with stage IV metastatic disease, we observed a progressive down-regulation of KAI1, from the normal adjacent colonic mucosa (KMS 193) to the primary tumor (KMS 72; P = 0.0001) to the liver metastasis (KMS 25; tumor compared with metastasis, P = 0.0135). We found no correlation between loss of KAI1 expression and stage of disease. In 10 patients, we also noted loss of KAI1 expression in the transition from normal colonic mucosa (KMS 237) to adenoma (KMS 174) to carcinoma (KMS 62; P < 0.0167 for all three comparisons). We conclude that the down-regulation of KAI1 occurs early in the progression of colorectal cancer.
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PMID:Loss of KAI1 expression in the progression of colorectal cancer. 1058 91

The KAI1 gene has been identified as a metastasis suppressor gene in human prostate cancer. Decrease or loss of KAI1/CD82 expression has been shown to be associated with poorer prognosis and metastasis in carcinomas of various organs. The purpose of this study was to examine whether KAI1/CD82 is expressed in bone and soft tissue tumors, and whether it is associated with metastasis to the lungs. Immunohistochemically, KAI1/CD82 expression in benign and malignant soft tissue tumors was noted in 83% and 37% of cases, respectively. KAI1/CD82 was- also expressed in benign bone tumors and osteosarcomas in 67% and 36% of the cases, respectively. Four (40%) of 10 osteosarcoma cases with no lung metastasis and one (25%) of four osteosarcoma cases with lung metastasis were positive for KAI1/CD82, respectively. Metastasis of osteosarcoma cells to the lungs was not correlated with the loss of KAI1/CD82 in osteosarcoma cells.
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PMID:Loss of KAI1/CD82 expression in bone and soft tissue tumors is not associated with lung metastasis. 1156 27

KAI1, which is identical to CD82, was initially identified as a metastasis-suppressor gene for human prostate cancer, and its expression is reported to be a favorable prognostic factor for operable human lung cancer. In this study, we examined the functional role of KAI1/CD82 in the late phase of metastatic spread of human lung-cancer cells. For this, KAI1/CD82 cDNA was introduced into KAI1/CD82 low-expressing human lung-cancer cell lines, SBC-3 and PC-14, and then the metastatic potential of the transformants was analyzed by i.v. inoculation of KAI1/CD82-transduced cells, SBC-3/KAI1 and PC-14/KAI1, into NK cell-depleted SCID mice. Contrary to our expectations, KAI1/CD82 gene transfer promoted multiorgan metastasis of i.v.-inoculated human lung-cancer cells, while s.c. tumor growth was unaffected. Cancer cells from metastatic tumors of NK cell-depleted SCID mice injected i.v. with SBC-3/KAI1 expressed appreciable cell-surface KAI1/CD82, and cells not expressing KAI1/CD82 (revertants) were not detected in the tumors. Our findings indicate that under conditions where the host's natural cytotoxicity is suppressed, KAI1/CD82 may enhance the formation of tumors by circulating lung-cancer cells at metastatic sites.
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PMID:Transduction of KAI1/CD82 cDNA promotes hematogenous spread of human lung-cancer cells in natural killer cell-depleted SCID mice. 1166 73

Because of the heterogeneous nature of prostate cancer, identifying the molecular mechanisms involved during the transition from an androgen-sensitive to an androgen-independent phenotype is very complex. An LNCaP cell model that recapitulates prostate cancer progression, comprising early passage androgen-sensitive (LNCaP-C33) and late passage androgen-independent (LNCaP-C81) phenotypes, would help to provide a better understanding of such molecular events. In this study, we examined the genes expressed by LNCaP-C33 and LNCaP-C81 cells using cDNA microarrays containing 1176 known genes. This analysis demonstrated that 34 genes are up-regulated and eight genes are down-regulated in androgen-independent cells. Northern blot analysis confirmed the differences identified by microarrays on several candidate genes, including c-MYC, c-MYC purine-binding transcription factor (PuF), macrophage migration inhibitory factor (MIF), macrophage inhibitory cytokine-1 (MIC-1), lactate dehydrogenase-A (LDH-A), guanine nucleotide-binding protein Gi, alpha-1 subunit (NBP), cyclin dependent kinase-2 (CDK-2), prostate-specific membrane antigen (PSM), cyclin H (CCNH), 60S ribosomal protein L10 (RPL10), 60S ribosomal protein L32 (RPL32), and 40S ribosomal protein S16 (RPS16). These differentially-regulated genes are correlated with progression of human prostate cancer and may be of therapeutic relevance as well as an aid in understanding the molecular genetic events involved in the development of this disease's hormone-refractory behavior.
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PMID:Expression profile of differentially-regulated genes during progression of androgen-independent growth in human prostate cancer cells. 1208 18

Current prognostic methods in primary prostate cancer cannot accurately identify patients with clinically significant disease at highest risk of developing metastases. This study examined KAI1/CD82 metastasis suppressor expression by quantitative immunohistochemical analysis of benign prostatic hyperplasia (BPH) and prostate cancer specimens. Altogether, prostate cancers exhibited significant KAI1 overexpression compared to BPH not associated with cancer (P = 0.022). Increased KAI1 expression in well and moderately differentiated cancers, above levels seen in BPH, with decreased expression in poorly differentiated cancers was observed. Interestingly, KAI1 expression in BPH associated with cancers was significantly higher than in BPH not associated with cancer (P = 0.009). Thus, KAI1 overexpression may restrain onset and early stage prostate cancer development, whilst its loss may predispose the patient to more aggressive cancer behaviour. Altered KAI1 expression in prostate cancers and BPH associated with cancer may have important diagnostic roles.
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PMID:KAI1/CD82 protein expression in primary prostate cancer and in BPH associated with cancer. 1208 6

To investigate the functional role of KAI1/CD82, a metastasis suppressor for human prostate cancer, in the regulation of homotypic cell adhesion, we transfected KAI1 cDNA into DU 145 human prostate cancer cells and established stable transfectant clones with high KAI1/CD82 expression. The KAI1 transfectant cells exhibited significantly increased homotypic cell aggregation in comparison with the control transfectant cells. This aggregation of the KAI1 transfectants was further enhanced upon exposure to anti-CD82 antibody, suggesting that KAI1/CD82 may be involved in the intracellular signaling for the cell adhesion. Among several signal pathway inhibitors tested, PP1, an inhibitor of Src family kinases, significantly suppressed homotypic aggregation of the KAI1 transfectant cells. Ligation of KAI1/CD82 with anti-CD82 antibody increased endogenous Src kinase activity of the KAI1 transfectant cells. When different types of src expression constructs were retransfected into the KAI1-transfected DU 145 cells, kinase-negative mutant src transfectant cells exhibited much lower homotypic aggregation than the mock cells transfected with an empty vector. Moreover, homotypic aggregation of the mutant src transfectant cells was not enhanced by KAI1/CD82 ligation with anti- CD82 antibody. These results suggest that Src mediates the intracellular signaling pathway of KAI1/CD82 for the induction of homotypic adhesion of human prostate cancer cells.
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PMID:Metastasis-suppressor KAI1/CD82 induces homotypic aggregation of human prostate cancer cells through Src-dependent pathway. 1264 1

KAI1/CD82 protein is a member of the tetraspanin superfamily and has been rediscovered as a cancer metastasis suppressor. The mechanism of KAI1/CD82-mediated suppression of cancer metastasis remains to be established. In this study, we found that migration of the metastatic prostate cancer cell line Du145 was substantially inhibited when KAI1/CD82 was expressed. The expression of focal adhesion kinase (FAK) and Lyn, a Src family tyrosine kinase and substrate of FAK, was up-regulated at both RNA and protein levels upon KAI1/CD82 expression. The activation of FAK and Lyn, however, remained unchanged in Du145-KAI1/CD82 cells. As a downstream target of FAK-Lyn signaling, the p130CAS (Crk-associated substrate) protein was decreased upon the expression of KAI1/CD82. Consequently, less p130CAS-CrkII complex, which functions as a "molecular switch" in cell motility, was formed in Du145-KAI1/CD82 cells. To confirm that the p130CAS-CrkII complex is indeed important for the motility inhibition by KAI1/CD82, overexpression of p130CAS in Du145-KAI1/CD82 cells increased the formation of p130CAS-CrkII complex and largely reversed the KAI1/CD82-mediated inhibition of cell motility. Taken together, our studies indicate the following: 1) signaling of FAK-Lyn-p130CAS-CrkII pathway is altered in KAI1/CD82-expressing cells, and 2) p130CAS-CrkII coupling is required for KAI1/CD82-mediated suppression of cell motility.
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PMID:Requirement of the p130CAS-Crk coupling for metastasis suppressor KAI1/CD82-mediated inhibition of cell migration. 1273 93

Cancer metastasis suppressor KAI1/CD82 belongs to the tetraspanin superfamily and inversely correlates with the metastatic potential of a variety of cancers. The mechanism of KAI1/CD82-mediated metastasis suppression remains unclear. In this study, we found a M(r) 68,00 cell-surface protein physically associated with KAI1/CD82 and named it KASP: a KAI1/CD82-associated surface protein. Distinctive from known KAI1/CD82 associations that usually occur in the context of "tetraspanin web," the KAI1/CD82-KASP association is likely to be direct because it is: (a) highly stoichiometric; (b) stabilized by chemical cross-linking; and (c) independent of cholesterol-enriched lipid rafts. Therefore, KASP is one of the major transmembrane proteins that associates with KAI1/CD82. Consistent with the wide distribution of KAI1/CD82, KASP is expressed ubiquitously in human tissues. Through peptide sequencing, KASP was identified as an immunoglobulin superfamily member called EWI2 or PGRL. Although EWI2/PGRL has been found to associate with tetraspanins CD9 and CD81, it forms distinct complexes with different tetraspanins, and its association with KAI1/CD82 could be independent of CD81 and CD9. Overexpression of EWI2/PGRL in Du145 metastatic prostate cancer cells inhibits cell migration on both fibronectin- and laminin-coated substratum, indicating that EWI2/PGRL directly regulates cell migration. Furthermore, EWI2/PGRL synergizes KAI1/CD82 in inhibiting cell migration, indicating that EWI2/PGRL is likely required for the function of KAI1/CD82. In summary, we identified a major KAI1/CD82-associated protein, EWI2/PGRL, that is important for KAI1/CD82-mediated suppression of cancer cell migration.
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PMID:EWI2/PGRL associates with the metastasis suppressor KAI1/CD82 and inhibits the migration of prostate cancer cells. 1275 Feb 95


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