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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This paper reviews the current advances in molecular genetics and biology of prostate cancer development. Many genetic alterations in prostate cancer have been identified. Some of these changes are early events and occur in prostatic intraepithelial neoplasia and primary cancer of prostate, some others occur in late stages of prostate cancer development. The significant genetic changes for prostate cancer include losses for chromosomes 8p, 5q, 13q, and so forth; gains for chromosomes 8q, 11p, 3q, and so forth; aneusomies of chromosomes 7 and 8; and allelic losses at chromosome regions 8p 12-21, 10q23-24, 16q22.1-24, and 7q31.1-31.2. The alteration of the p53 tumor-suppressor gene plays a role in a subset of advanced prostate cancer. Expressions of TGF-beta receptors, E-cadherin, C-CAM, KAI1, and some integrins have an inverse correlation with either prostatic carcinogenesis or progression of prostate cancer, or both. Protein expression of BCL-2 in prostate cancer is highly correlated with cancer progression and androgen-independent phenotype. More studies need to be performed to identify specific genes for those genetic alterations and to explore the clinical use of the known molecules in prostate cancer.
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PMID:Molecular advances in prostate cancer. 909 May 1

KAI1 is a tumor metastasis suppressor gene that is capable of inhibiting the metastatic process in animals. The expression of the KAI1 gene also is found to be down-regulated during the tumor progression of prostate, breast, lung, bladder, and pancreatic cancers in humans, and this down-regulation appears to be at or posttranscription level. We have found that the tumor suppressor gene p53 can directly activate the KAI1 gene by interacting with the 5' upstream region. The p53 responding region is located at approximately 860 bases upstream of the transcriptional initiation site, and it contains a typical tandem repeat of the p53 consensus-binding sequence. A gel-shift mobility analysis showed that this sequence indeed had the ability to bind to the purified p53 protein. Mutations of this sequence abolished the responsiveness to p53 and also the binding ability to the p53 protein. Furthermore, immunohistochemical analysis of 177 samples of human prostate tumors revealed that the expression of the KAI1 gene was correlated strongly to that of the p53 gene and that the loss of these two markers resulted in poor survivals of patients. Our data indicate a direct relationship between p53 and KAI1 genes and suggest that the loss of p53 function, which is commonly observed in many types of cancer, leads to the down-regulation of the KAI1 gene, which may result in the progression of metastasis.
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PMID:The expression of the KAI1 gene, a tumor metastasis suppressor, is directly activated by p53. 973 32

Several members of the transmembrane 4 superfamily (TM4SF) have been reported to be related to tumor progression and metastasis. The aims of our study were to clarify the relationship between TM4SF and pancreatic cancer and to determine the prognostic significance of TM4SF in human pancreatic cancer. The mRNA levels for MRP-1/CD9, KAI1/CD82 and ME491/CD63, which belong to the TM4SF gene family, were evaluated in 40 resectable pancreatic adenocarcinomas using reverse transcriptase-PCR. MRP-1/CD9 gene expression was associated with lymph node status, and with pathological status. Moreover, MRP-1/CD9 expression was inversely associated with histo-pathological grading. KAI1/CD82 gene expression was inversely associated with tumor status. ME491/CD63 gene expression, however, was conserved in all pancreatic cancers. The overall survival rate for the 22 patients whose tumors had decreased MRP-1/CD9 gene expression was strikingly lower than that for the 18 patients with MRP-1/CD9-positive tumors. The overall survival rate of the 15 patients who were KAI1/CD82-positive was significantly higher than that of the 25 patients with decreased KAI1/CD82 gene expression. In a multivariate analysis using the Cox proportional hazards model, MRP-1/CD9 and KAI1/CD82 status was found to be the most significant.
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PMID:Transmembrane 4 superfamily as a prognostic factor in pancreatic cancer. 976 Nov 21

KAI1, a metastasis suppressor gene of prostate cancer, is located on human chromosome 11p11.2. Down-regulation of KAI1 mRNA during tumor progression and metastasis has been reported for several kinds of cancer, but the mechanism of this down-regulation is not known. In the present study, our aim was to ascertain the relationship between down-regulation of KAI1 mRNA expression and KAI1 gene alterations in lung cancer. Forty-nine cases of adenocarcinoma of the lung were studied by reverse-transcriptase polymerase chain reaction (RT-PCR) assay of KAI1 mRNA and by immunohistochemical detection of KAI1 protein. In addition, markers of the microsatellite loci D11S1344 and D11S1326 were used to investigate loss of heterozygosity (LOH) and replication errors (RERs) of the KAI1 gene region. The RT-PCR assay showed that there was no correlation between KAI1 mRNA expression and either the age of the patients or tumor size. By contrast, KAI1 mRNA expression was significantly correlated with gender (P=0.047), metastasis to the lymph nodes or other organs (P=0.004), the histological grade of the tumor (P=0.036) and the pathological stage (P=0.049). Immunohistochemical staining showed that in one case without metastasis, loss of KAI1 mRNA was associated with invasion of the stroma by KAI1 protein-negative cancer cells. The numbers of informative cases by microsatellite analysis were 14 (28.6%) of 49 at D11S1344 and 27 (55.1%) of 49 at D11S1326; none of 49 adenocarcinomas showed LOH or RERs at these loci. These results suggest that down-regulation of KAI1 mRNA expression rarely if ever involves LOH or RERs of the KAI1 gene region in primary lung adenocarcinoma.
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PMID:Down-regulation of KAI1 messenger RNA expression is not associated with loss of heterozygosity of the KAI1 gene region in lung adenocarcinoma. 1055 26

KAI1/CD82 has been shown to be a metastasis suppressor for several human cancers, and a recent study revealed that wild-type tumor suppressor p53 can directly activate KAI1/CD82 gene expression. However, the response of KAI1/CD82 expression in cancer cells to exogenous stimulants has not been investigated. The present study examined whether tumor necrosis factor (TNF), which mediates many of the cellular responses associated with inflammatory reactions or cancer progression, can affect the KAI1/CD82 expression in lung cancer cells and, if so, whether nuclear factor (NF)-kappaB, a key molecule in TNF-mediated gene expression, is involved in the mechanism of KAI1/CD82 induction. Our results demonstrated that expression of KAI1/CD82 in PC-14 cells expressing mutant p53 could be augmented by TNF-alpha, and that transfer of the gene for a specific inhibitor of NF-kappaB, IkappaB alphaSR (mutant IkappaB alpha; NF-kappaB super-repressor), into PC-14 cells could inhibit this augmentation. The amount of NF-kappaB in the nucleus of PC-14/IkappaB alphaSR cells correlated well with KAI1/CD82 mRNA and protein expression. In addition, IkappaB alphaSR gene transfer inhibited the spontaneous expression of KAI1/CD82 protein in KAI1/CD82-high-expressing RERF-LC-OK cells, which contain a mutant-type p53. These observations indicate that NF-kappaB activation may play a role in the regulation of KAI1/CD82 expression in lung cancer cells independently of wild-type p53, and suggest that KAI1/CD82 expression may be regulated by interaction with the host microenvironment.
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PMID:Nuclear factor-kappaB-dependent expression of metastasis suppressor KAI1/CD82 gene in lung cancer cell lines expressing mutant p53. 1121 67

Transmembrane 4 superfamily (TM4SF) is a recently described gene family, and TM4SF members are known to play roles in the signal transduction pathways and to regulate cell activation, development, proliferation, and motility. MRP-1/CD9, KAI1/CD82, and ME491/CD63, members of the TM4SF, have been reported to suppress tumor progression or metastasis. Previously, we showed that MRP-1/CD9 suppressed cell motility and metastatic potential to lungs. Moreover, reduction of MRP-1/CD9 and KAI1/CD82 gene expression was found to be a factor in a poor prognosis for patients with non-small cell lung cancer. However, among TM4SF, CD151 is identical to an existing gene, PETA-3, which may promote tumor metastasis of malignant cells, and its expression may be involved in the malignant progression of cancer. The function of CD151 is opposite that of the metastasis suppressor genes, MRP-1/CD9 and KAI1/CD82. On the basis of these results, we used reverse transcription-PCR and immunohistochemical techniques for a retrospective study of CD151 gene expression in tumor tissues from 145 lung cancer patients; 72 tumors were stage I, 29 stage II, 27 stage IIIA, and 17 stage IIIB. Whereas 86 patients had tumors positive for the CD151 gene, 59 had tumors that were negative for the CD151 gene. The overall survival rate of patients with CD151-positive tumors was much lower than that of CD151-negative patients (51.9% versus 73.1%; P = 0.013). Our findings suggest that high CD151 gene expression in lung cancer may be associated with a poor prognosis. Assessment of CD151 could be instrumental for improvements in lung cancer diagnosis and therapies.
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PMID:Clinical significance of CD151 gene expression in non-small cell lung cancer. 1175 9

Pancreatic cancer has one of the poorest prognoses of all gastrointestinal malignancies. Today, it is the fourth or fifth leading cause of cancer-related deaths in Western industrialized countries, and the incidence has been increasing throughout the past decades. Insensitivity to growth-inhibitory and apoptotic signals as well as self-sufficiency of growth-promoting factors are hallmarks of the pathogenesis of this malignancy. In pancreatic cancer, a variety of growth factors and their receptors are expressed at increased levels. For example, the concomitant presence of the epidermal growth factor (EGF) receptor and its ligand EGF is associated with enhanced tumor aggressiveness and shorter survival following tumor resection. Furthermore, a number of other growth factors and their receptors, such as nerve growth factor and its receptor, are overexpressed in pancreatic cancer and contribute to its malignant phenotype. Besides factors which directly promote cell proliferation, a variety of other factors such as galectins are upregulated, which influences the tumor environment and the invasiveness of pancreatic cancer cells. In addition, tumor suppressor genes such as KAI1 are expressed at reduced levels, thereby enhancing the ability of pancreatic cells to form metastases. A complex disturbance of factors is present in pancreatic cancer, resulting in a distinct growth advantage which clinically results in rapid tumor progression and poor patient survival.
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PMID:Pancreatic cancer: factors regulating tumor development, maintenance and metastasis. 1212 Feb 31

The disease progression and rate of cancer death were analyzed in 52 patients with stage A prostate cancer who underwent transurethral resection of the prostate (TURP) or retropubic subcapsular prostatectomy (SCP) between 1987 and 1998. We performed immunohistochemistry on 16 patients to determine the correlation between the expression of the tumor metastasis suppressor gene KAI1 and the subsequent progression of stage A prostate cancer. Nineteen and 33 of the patients had cancer at stage A1 and stage A2, respectively, and their subsequent courses were followed for an average of 53.7 months (24-134 months). Progression to clinical cancer was found in six patients (one with stage A1, and five with stage A2). This progression was evident 40.8 months (5-80 months) after TURP or SCP. Four (66.7%) of the patients died of cancer progression (average 31 months) after prostatectomy. All four patients had stage A2, poorly differentiated adenocarcinoma, and had been followed with administration of diethylstilbestrol diphosphate (DES-P). The disease-free patients (n=10) showed overexpression of KAI1 protein, compared to those with disease progression (n=6). These results indicate that progression arose mainly in the patients with stage A2 cancer, and that poorly differentiated, focal and weak expression of KAI1 protein is highly associated with disease progression. It is suggested that patients in this group should be treated with immediate total androgen blockade, radiation, or radical prostatectomy after diagnosis.Prostate Cancer and Prostatic Diseases (2001) 4, 150-153.
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PMID:KAI1 expression can be a predictor of stage A prostate cancer progression. 1249 33

Recent data have proposed that transcription of the KAI1 metastasis suppressor gene is directly mediated by p53 and that loss of KAI1 expression in advanced prostate cancer is simply due to loss of p53 function after mutation. To investigate this possibility, we have examined KAI1 mRNA (by in situ hybridisation) and p53 protein expression (by immunohistochemistry) as an indicator of wildtype or mutant p53, in a series of 77 paraffin-embedded prostate tissue samples, including post-mortem normal prostates (2), benign prostatic hyperplasia (10), localised cancer (grades 4-6, 25; grades 7-9, 21) and prostate-derived bony metastases (19). Overall, we confirmed that expression of KAI1 mRNA decreased from normal tissue, through localised cancer to bony metastases (P=0.055, tending to significance), while levels of p53 staining significantly increased with cancer progression (P=0.046). These were consistent with the possibility that loss of p53 function might be responsible for loss of KAI1 mRNA. However, by close examination of KAI1 and p53 in adjacent tissue sections, we found no correlation between decreased levels of KAI1 mRNA and overexpression of p53 protein (P=0.497). In addition, high levels of KAI1 mRNA could be identified in samples irrespective of p53 staining. Our data suggest that mutation of p53 is independent of the loss of KAI1 mRNA, and do not support a role for p53 in regulating the expression of KAI1.
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PMID:Downregulation of KAI1 mRNA in localised prostate cancer and its bony metastases does not correlate with p53 overexpression. 1280 79

Tumors of the gastrointestinal tract -- gastric, colorectal, pancreatic and liver tumors -- account for over 50 % of cancer worldwide. The 5-year survival rate varies from > 50 % in colorectal to < 1 % in pancreatic cancer. The high cancer death rate strikingly correlates with the high metastasizing capacity of most gastrointestinal tumors. Therefore and because during the last decade several important hypotheses on metastasis formation could be settled on solid experimental ground, this review will first provide a brief outline on the currently most accepted view of tumor progression and then discuss whether and how the rather new family of tetraspanin molecules might contribute to cancer progression. Notably, some members of this family, in particular, CD82/KAI1 are known as metastasis suppressor genes, while others like CD151 and CO-029 are supposed to promote metastasis formation. The underlying mechanisms are beginning to become unraveled. Tetraspanins assemble complexes of different tetraspanins, integrins and additional transmembrane molecules in microdomains that serve as signaling platform. By creating proximity, tetraspanins modulate functional activity of the associating molecules. In addition, tetraspanins actively contribute to the intracellular traffic of the associating molecules that includes vesicular budding and formation of exosomes that are particularly rich in tetraspanins. Accordingly, the association of certain tetraspanins with the metastatic phenotype as well as the definition of other tetraspanins as metastasis suppressor genes has to be viewed from the perspective of molecular complexes rather than the individual tetraspanin.
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PMID:Gastrointestinal tumors: metastasis and tetraspanins. 1682 99


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