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)

The KAI1 gene, located on human chromosome 11p11.2, suppresses tumor metastasis when expressed in certain cancer cells. To evaluate whether dysregulation of KAI1 occurs during the progression of human prostatic cancer, protein expression, mutation, and allelic loss of KAI1 were analyzed using a tissue bank of 98 primary cancers and 32 metastases. By immunohistochemical staining, high levels of KAI1 protein are detected in the epithelial but not stromal compartment of normal prostatic and benign prostatic hyperplasia tissue. In epithelial cells, KAI1 protein is expressed on the plasma membrane. KAI1 protein expression is downregulated in more than 70% of the 49 primary prostatic cancers from untreated patients. In 10 such untreated patients, down-regulation of KAI1 protein occurred in all of the lymph node metastases examined. In 15 patients with metastatic disease who had failed androgen ablation therapy, more than 90% of the primary prostatic cancers had downregulation, with 60% having no KAI1 protein expression. Primers derived from the sequences flanking each exon of KAI1 were used to analyze KAI1 mutation and allelic loss by the method of PLR-single-strand conformational polymorphism. Using this method, no point mutation or allelic loss was detected in metastases from 10 patients. No allelic loss was detected in an additional 34 primary and 12 lymph node metastases via microsatellite analysis using the marker D11S1344, which is located in the region of KAI1. These results demonstrate that KAI1 protein expression is consistently down-regulated during the progression of human prostatic cancer and that this down-regulation does not commonly involve either mutation or allelic loss of the KAI1 gene.
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PMID:Down-regulation of the KAI1 metastasis suppressor gene during the progression of human prostatic cancer infrequently involves gene mutation or allelic loss. 881 31

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 KAI1 gene, isolated from human chromosome 11p11.2, has been implicated as a prostate cancer metastasis suppressor gene. Recent studies have demonstrated that the expression of KAI1 protein is reduced in metastases of human prostate cancers and is inversely correlated with tumour grade. The objectives of the present work were to determine whether alterations of KAI1 at a genetic level in localized prostate cancers correlate with degrees of differentiation. This paper reports the application of semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Southern analysis to two different regions of the KAI1 gene on 35 microdissected primary prostate cancer specimens and demonstrates a biphasic pattern of KAI1 expression according to histological grade. KAI1 mRNA, relative to the housekeeping gene beta -actin, was elevated in low-grade primary prostate cancer (2.7+/-0.4) compared with non-malignant (hyperplastic) prostatic tisues (0.92+/-0.02, p< 0.05), yet reduced in high-grade primary cancers (0.61+/-0.11, p< 0. 05). These data demonstrate, for the first time, that KAI1 is biphasically expressed in primary prostate cancers and suggest that hyperexpression of KAI1 in low-grade prostate cancer may be associated with restraint of tumour progression, whereas a relative decrease in KAI1 gene expression may accompany more aggressive cancers through loss of such restraint. This differential expression of the metastasis suppressor gene KAI1 in primary prostate cancers may have important prognostic implications for the development of subsequent metastases. Should the level of KAI1 in primary prostate cancer be correlated with patient outcome such information may, in the future, enable more intensive adjuvant therapy to be directed to those patients identified to be at greatest risk of metastasis.
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PMID:Expression of the prostate cancer metastasis suppressor gene KAI1 in primary prostate cancers: a biphasic relationship with tumour grade. 1044 Jul 48

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

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 was identified as a metastasis suppressor gene for human prostate cancer. Recently, we showed that KAI1 mRNA levels were higher in an immortal, normal-like breast epithelial cell line and nonmetastatic breast cancer cell lines but lower substantially in highly metastatic breast cancer cell lines. In this study, we examined KAI1 protein expression in breast cancer cell lines by Western blot and immunohistochemical study. KAI1 protein levels paralleled KAI1 mRNA levels and were inversely correlated with the metastatic potential of breast cancer cells. Furthermore, we examined KAI1 protein expression immunohistochemically in specimens from 81 patients with breast cancer and then correlated the findings with the clinical and histopathological parameters of the patients. High levels of KAI1 protein expression were found in normal breast tissues and noninvasive breast cancer (ductal carcinoma in situ). In contrast, KAI1 expression was reduced in most of the infiltrating breast tumors. We found that, in general, more malignant tumors demonstrated significantly lower KAI1 expression (P = 0.004). Additionally, among 29 specimens demonstrating multiple stages of malignancy within a single specimen, 23 demonstrated significant differences in KAI1 expression between benign breast tissue, ductal carcinoma in situ, and invasive carcinoma. The higher the incidence for malignancy within a given specimen, the lower the KAI1 expression (P < 0.001). These data suggest that in advanced breast cancer, KAI1 expression is down-regulated. Therefore, KAI1 may be a potentially useful indicator of human breast cancer progression.
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PMID:KAI1 protein is down-regulated during the progression of human breast cancer. 1099 24

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.
Prostate Cancer Prostatic Dis 2001
PMID:KAI1 expression can be a predictor of stage A prostate cancer progression. 1249 33