非小细胞肺癌中KAI1基因表达及其与P53的相关性研究

背景与目的近年研究表明,KAI1表达下调与多种肿瘤的转移有关,但其与非小细胞肺癌的关系研究较少,且导致其下调的机制尚未明确。本研究从mRNA和蛋白水平探讨KAI1基因在非小细胞肺癌组织中的表达与患者临床病理特征的关系及其与突变型P53蛋白表达的关系。方法采用RTPCR和Westernblot法,检测48例肺癌患者手术切除的新鲜癌组织标本中KAI1mRNA、KAI1/CD82及突变型P53蛋白的表达,20例肺部良性疾病组织和正常肺组织作为对照。结果肺癌组和对照组中KAI1mRNA的阳性率分别为52%和90%(P<0.01),KAI1/CD82蛋白的阳性率分别为48%和85%(P<0.01),突变型P53蛋白阳性率分别为65%和5%(P<0.01)。KAI1mRNA、KAI1/CD82和突变型P53蛋白阳性率与肺癌患者临床分期、细胞分化程度和淋巴结转移有密切关系(P<0.05或P<0.01)。肺癌组织中KAI1mRNA与KAI1/CD82表达呈密切相关性(P<0.01),KAI1/CD82与突变型P53蛋白的表达亦呈显著相关性(P<0.05),KAI1mRNA与突变型P53表达无明显相关性(P>0.05)。结论KAI1基因的低表达可能与非小细胞肺癌的发生、发展和转移有关;其下调的机制可能主要发生在转录水平并与p53基因有关,二者可能作为评估肺癌患者转移潜能的指标。     

Loss of KAI1 expression in the progression of colorectal cancer

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.     

KAI1基因在非小细胞肺癌中的表达及意义

 目的 探讨肿瘤转移抑制基因KAI1基因在非小细胞肺癌组织中的表达及其与患者临床病理指标的关系。 方法 采用RT-PCR和Western blot法,检测48例肺癌患者手术切除的新鲜肺癌组织标本和20例同期手术切除的肺部良性病变周围正常组织中KAI1 mRNA、KAI1/CD82,并结合患者的临床病理资料对其结果进行统计分析。 结果 肺癌组织和肺部良性病变组织中KAI1 mRNA的阳性率分别为52%和90%,KAI1/CD82蛋白的阳性率分别为48%和85%,肺癌组KAI1mRNA及KAI1/CD82蛋白表达均低于肺部良性病变组（P<0.01）;KAI1mRNA、KAI1/CD82表达水平与肺癌患者的临床分期、组织分化程度、淋巴结转移有关（P<0.05）,其中KAI1/CD82表达与淋巴结转移状况密切相关(P<0.01),肺癌组织中KAI1 mRNA与KAI1/CD82表达有相关性（P<0.01）。 结论 KAI1基因的低表达可能与非小细胞肺癌的发生、发展和转移有关;其下调的机制可能主要发生在转录水平;KAI1基因的表达可作为一项评估肺癌患者转移潜能的指标。     

KAI1 metastasis suppressor protein is down-regulated during the progression of human endometrial cancer.

PURPOSE: KAI1 is a metastasis suppressor gene located on human chromosome 11p11.2. It is a member of the structurally distinct family of cell surface glycoprotein, transmembrane 4 protein superfamily. KAI1 was initially isolated as a gene that suppressed metastasis of rat prostate tumor cells. Decreased KAI1 expression has been observed recently in various human cancers, including pancreatic, lung, hepatic, colorectal, breast, ovarian, esophageal, and cervical cancers. Frequent down-regulation of the KAI1 protein was also observed in endometrial cancer cell lines. The aim of this study was to determine whether this gene is altered in human endometrial carcinoma. In addition, its prognostic significance in this tumor was also evaluated. EXPERIMENTAL DESIGN: Tumor specimens from 18 cases with various degrees of endometrial hyperplasia, 97 primary endometrial carcinomas with various stages, and 28 metastatic lesions of this cancer were examined in this study. Using the method of immunohistochemistry, we characterized the KAI1 protein expression in the 143 endometrial tumors. Expression of KAI1 at RNA level was also examined in 35 of the 143 samples using a real-time quantitative PCR method. The data from immunohistochemical analysis were correlated with various clinicopathological factors. RESULTS: High levels of KAI1 protein expression were detected in almost all of the specimens with endometrial hyperplasia (17 of 18). In contrast, loss of KAI1 expression occurred in an increasing frequency (27.8-71.4%) from early stages of primary endometrial carcinomas to metastatic tumors (P < 0.001). In addition, more poorly differentiated tumors demonstrated significantly lower KAI1 expression as compared with the well-differentiated tumors (P < 0.001). It was also found that patients with KAI1-negative tumors had a lower survival rate than those with KAI1-decreased or positive tumors (P = 0.0042 and 0.0286, respectively). However, in multivariate analysis, the prognostic significance of KAI1 expression was inferior to tumor stage. CONCLUSION: These data suggest that KAI1 expression is down-regulated in advanced endometrial cancer. Clinically it may be a useful indicator of the tumor progression and may provide prognostic information on the outcome of this disease.     

口腔鳞癌组织中KAI1 mRNA的表达

目的:探讨肿瘤转移抑制基因KAI1 mRNA在口腔鳞状细胞癌中的表达及其临床病理意义。方法:采用原位杂交法检测74例原发性口腔鳞癌(无淋巴结转移49例,有淋巴结转移25例)、21例相应的淋巴结转移灶、19例口腔黏膜白斑和10例正常口腔黏膜石蜡标本组织中KAI1 mRNA的表达情况。结果:KAI1 mRNA在正常黏膜组、黏膜白斑组、鳞癌无淋巴结转移组、有淋巴结转移组和淋巴结转移灶组中阳性表达率分别为100%、84.2%、61.2%、28.0%和4.8%,其中无淋巴结转移鳞癌组显著低于正常和黏膜白斑组,P<0.05,淋巴结转移组显著低于无淋巴结转移组,P=0.045,淋巴结转移灶组显著低于相应鳞癌组,P=0.040。低分化鳞癌的KAI1阳性表达率显著低于高、中分化鳞癌,P<0.001。KAI1的表达与鳞癌患者的年龄、性别、肿瘤大小和浸润深度以及pT-MN分期无显著相关,P>0.05。结论:KAI1 mRNA表达下调可能与口腔鳞状细胞癌的组织分化程度和淋巴结转移有关。     

KAI1/CD82 expression as a prognosic factor in sporadic colorectal cancer

BACKGROUND: Since its identification as a suppressor gene for prostate cancer metastasis, down-regulation of KAI1/CD82 in a variety of malignancies has been reported. MATERIALS AND METHODS: Using immunohistochemistry, we examined KAI1/CD82 expression in surgical specimens obtained from 70 patients with advanced colorectal cancer and its correlation with clinicopathological factors, to clarify their prognostic significance. RESULTS: KAI1/CD82 expression was positive in 55% of the 70 colorectal cancers. There were statistically significant correlations between KAI1/CD82 expression and Dukes' stage, venous invasion, lymph node metastasis, tumor differentiation and liver metastasis. The significant correlation between KAI1/CD82 expression and outcome among patients with Dukes' C cancer (p=0.024) is particularly noteworthy. On multivariate analysis, KAI1/CD82 expression and Dukes' stage were identified as significant and independent prognostic factors (p=0.006 and 0.045, respectively). CONCLUSION: KAI1/CD82 expression closely correlates with clinicopathological factors for colorectal cancers. KAI1/CD82 expression appears to be a useful prognostic marker.     

nm23-H1基因在喉癌中杂合性丢失和微卫星序列不稳定性分析及表达的研究

目的　探讨nm2 3 H1基因在喉鳞状细胞癌中杂合性丢失 (LOH)及表达情况。方法　选择nm2 3 H1基因内部及附近 5个微卫星多态标记 ,对 72例喉癌标本进行杂合性丢失和微卫星序列不稳定性检测 ,同时以RT PCR方法分析 38例配对喉鳞状细胞癌标本中nm2 3 H1基因表达情况。结果　LOH涉及至少 1个位点的频率高达 76 .39% ,5个位点均有LOH ,以D17S16 6 5处频率最高 ,达 38.10 %。 3个位点出现MI ,最高为 12 .70 %。nm2 3 H1基因杂合性丢失及微卫星不稳定与淋巴结转移、临床分期和肿瘤分化无显著相关性 (P >0 .0 5 ) ,但D17S16 6 5位点高LOH频率与低分化相关 (P <0 .0 5 )。癌、癌旁及转移淋巴结中nm2 3 H1表达不同 ,但差异无统计学意义 ,表达水平与淋巴结转移无关 (P >0 .0 5 )。结论　nm2 3 H1基因可能在喉鳞癌发生中起作用 ,杂合性丢失可能是影响基因功能的主要机制。     

Clinical implications of mRNA expression of KAI1 in ovarian cancer with or without metastasis

Background. KAI1 is a potential metastasis suppressor gene for prostate cancer. Decreased expression of KAI1 mRNA has been shown to be associated with the formation of metastasis and the progression of prostate, lung, breast, pancreatic, and bladder cancer. It has also been reported, however, that KAI1 expression is unchanged in metastatic and nonmetastatic esophageal and gastric cancer. We performed the present study to investigate the function of KAI1 in the progression and/or metastasis of ovarian cancer. Methods. We investigated the mRNA expression levels of the KAI1 gene, using quantitative polymerase chain reaction (PCR), in 29 ovarian tumors (1 adenoma, 2 low- malignant potential tumors, 9 adenocarcinomas without metastasis, and 17 adenocarcinomas with metastasis), seven ovarian cancer cell lines, and two normal ovaries. Using a thermal cycler, we found that the KAI1 gene was amplified in parallel with an internal control gene, β-Actin. The relative expression ratio (KAI1/β-Actin) as measured by densitometry was used to evaluate gene expression. Immunohistochemical localization of the KAI1 protein in ovarian cancer tissues was confirmed by the avidin-biotin peroxidase complex (ABC) method. Results. The mRNA expression levels of KAI1 were consistent in normal ovary, ovarian tumor samples, and ovarian cancer cell lines. No statistically significant difference in the KAI1 mRNA expression level was found in ovarian cancer samples with or without metastasis. Immunohistochemistry revealed that the KAI1 protein was expressed in the cell membranes of ovarian cancer cells. Conclusions. Our results suggest that reductions in KAI1 mRNA expression are not involved in either the progression or metastasis of ovarian carcinomas. Received: April 22, 1999 / Accepted: July 26, 1999     

应用组织芯片技术检测KAI1、MRP-1、FAK蛋白在肺癌组织中的表达

背景与目的:肿瘤的发生发展、浸润转移与多基因改变密切相关。目前Kang-ai-1(KAI1)、移动相关蛋白(motility-relatedprotein-1,MRP-1)和局部粘着斑激酶(focaladhesionkinase,FAK)3种基因在肺癌中的共同作用研究较少。本研究旨在探讨这3种基因的蛋白产物在肺癌发生发展中的作用及其在肿瘤诊断和预后判断中的价值。方法:应用免疫组化SP方法检测包含240个点的肺癌组织芯片中KAI1、MRP-1和FAK蛋白的表达。结果:KAI1在肺癌原发灶中阳性率为25.9%,MRP-1为42.6%,与正常肺组织(100%)相比均显著下调;FAK蛋白在肺癌组织中阳性率为44.4%,与正常肺组织相比显著增高;KAI1、FAK两种蛋白在肺癌组织中的表达与患者的年龄、性别、肿瘤的大体类型及组织类型无关,而与肿瘤的分化程度、临床分期及是否伴有淋巴结转移密切相关,两种蛋白的表达呈显著负相关。MRP-1蛋白在肺癌组织中的表达与组织类型有关,小细胞肺癌与非小细胞肺癌相比差异显著,MRP-1与KAI1呈显著正相关,与FAK呈显著负相关。结论:KAI1、MRP-1和FAK的异常表达与肺癌的浸润转移有关,联合检测这3项指标对肺癌的发生发展有重要的预测作用。     

KAI1 protein is down-regulated during the progression of human breast cancer.

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.     

Mutation and expression of the metastasis suppressor gene KAI1 in esophageal squamous cell carcinoma

BACKGROUND: KAI1/CD82, a tumor metastasis suppressor gene, is correlated inversely with the progression and invasion of several tumors. It also has been reported that the KAI1 gene is related to the tumor suppressor gene p53. This study was performed to clarify the correlation between KAI1/CD82 expression and clinicopathologic characteristics and p53 expression in patients with esophageal squamous cell carcinoma (ESCC). The authors also investigated mutation of the KAI1 gene coding region to determine whether this may reduce KAI1 expression in ESCC. METHODS: Using immunohistochemistry with anti-KAI1 polyclonal antibody and monoclonal antibody against p53, KAI1/CD82 and p53 expression were detected in 55 patients with ESCC who had undergone surgery. The authors examined the KAI1 gene mutation in 22 patients with ESCC by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis and DNA sequencing. RESULTS: KAI1/CD82 expression was positive in 36 of 55 patients (65.5%). There was a significant inverse correlation between KAI1/CD82 expression and regional lymph node metastasis (P = 0.0045), distant metastasis (P = 0.0092), the number of lymph node metastases (P = 0.0019), and pathologic stage (P = 0.0046). The survival rates of KAI1/CD82 negative patients were poorer than those of positive patients (P = 0. 024). The correlation between KAI1 positive and p53 positive tumors was not statistically significant. None of the 22 patients with ESCC showed mutation of the KAI1 gene by PCR-SSCP. In one patient, there was polymorphism in the SSCP assay and DNA sequencing. CONCLUSIONS: The authors demonstrated immunohistochemically that the expression of KAI1 protein appeared to be correlated with lymph node metastasis. Mutation does not seem to be a mechanism for dysregulation of the KAI1 protein in ESCC.     

Nuclear factor-kappaB-dependent expression of metastasis suppressor KAI1/CD82 gene in lung cancer cell lines expressing mutant p53

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.     

KAI1/CD82在神经母细胞瘤组织中的表达及其与预后的关系

背景与目的KAI1/CD82是近年来发现的肿瘤转移抑制基因,它的失活与某些肿瘤的进展和浸润有关。本研究旨在通过检测KAI1/CD82蛋白在神经母细胞瘤中的表达,探讨其与神经母细胞瘤临床病理特征和预后的关系。方法用免疫组化EnVision法检测90例神经母细胞瘤瘤组织中KAI1/CD82蛋白的表达,结合临床资料与随访资料进行统计学分析。结果39.3%(11/28)节细胞神经母细胞瘤KAI1/CD82呈阳性表达,14.5%(9/62)神经母细胞瘤KAI1/CD82呈阳性表达(P=0.014)。KAI1/CD82的表达与神经母细胞瘤的分化程度呈显著性正相关,且KAI1/CD82的表达与临床分期呈显著性负相关(P=0.003)。结论KAI1/CD82表达的改变是神经母细胞瘤发生的早期事件,其表达下调是神经母细胞瘤分化和转移的一个潜在标志。此标记物可能作为临床评估预后的综合指标之一。     

KAI1/CD82 is a novel target of estrogen receptor-mediated gene repression and downregulated in primary human breast cancer

The cell-surface glycoprotein KAI1 suppresses tumor growth and metastasis in various animal models. Downregulation of KAI1 has been implicated in the progression of cancer. However, the mechanisms of KAI1 inactivation are poorly understood. This is the first study that investigates expression and regulation of KAI1 in human breast cancer. KAI1 expression was analyzed on custom-made tissue microarrays comprising 209 well-characterized breast cancers and normal mammary gland tissue. Strong KAI1 immunoreactivity was observed throughout the normal mammary gland epithelium. In breast cancer tissue, KAI1 immunoreactivity was lost in 161/209 (77%) cases. Strikingly, KAI1 was preferentially lost in estrogen receptor (ER)-positive breast cancers (p < 0.001). This was validated by real-time RT-PCR analyses showing a 7.5-fold downregulation of KAI1 mRNA in ER-positive relative to ER-negative tumors (p = 0.028). Notably, this was also corroborated by Affymetrix microarray expression data of an independent cohort of 49 breast cancers. Class comparison analysis identified KAI1 as downregulated in ER-positive tumors. Subsequently, human breast cancer cell lines were employed to test a potential role of ER-activity in the downregulation of KAI1, as suggested by our expression analyses. Exposure of ER-positive breast cancer cells to fulvestrant, a clinically approved ER-antagonist that reverses ER-mediated gene repression, induced a significant upregulation of KAI1 and inhibited cell proliferation as well as migration. In summary, we demonstrate for the first time that KAI1 is a target of ER-mediated gene-repression, and thus, it is downregulated in ER-positive breast cancer. Importantly, KAI1 might be reinducible by endocrine therapy with ER-antagonists in patients suffering from ER-positive breast cancer.     

Overexpression of KAI1 suppresses in vitro invasiveness and in vivo metastasis in breast cancer cells.

KAI1 is a metastasis suppressor gene for human prostate cancer and is also involved in the progression of a variety of other human cancers. Previously, we have demonstrated that KAI1 expression was down-regulated in metastatic breast cancer cell lines as well as in highly aggressive breast cancer specimens. To determine whether KAI1 expression is responsible for the metastasis suppression in breast cancer, we transfected the human KAI1 cDNA into two highly malignant breast cancer cell lines, LCC6 and MDA-MB-231, which both have low levels of endogenous KAI1 expression. Parental, vector-only transfectants and KAI1 transfectant clones were injected into the mammary fat pads and tail veins, respectively, of athymic nude mice and assessed for both spontaneous and experimental lung metastasis. High KAI1 expression significantly suppressed the metastatic potential of KAI1-transfected LCC6 cells. Metastasis suppression correlated with the reduced rate of tumor growth and a decreased clonogenicity in soft agar. Furthermore, KAI1 expression significantly suppressed the in vitro cell invasion in KAI1-transfected MDA-MB-231 cells. Our results suggested that KAI1 may function as a negative regulator of breast cancer metastasis.     

KAI1基因表达与大肠癌发生、发展的关系

 目的 探讨KAI1基因的表达与大肠癌(CRC)发生、发展的关系. 方法 采用RT-PCR法及免疫组织化学(EnvisionTM法)检测40例大肠癌组织、8例癌旁黏膜和8例正常黏膜的KAI1 mRNA和蛋白表达. 结果 正常黏膜KAI1 mRNA水平显著低于癌组织(P<0.05),癌旁黏膜略高于正常黏膜,但无显著差异;在大肠癌原发灶中,KAI1蛋白表达阳性25例(62.5%),弱阳性9例(22.5%),阴性6例(15%).KAI1 mRNA及蛋白水平在低分化、伴淋巴结转移肿瘤中表达显著降低(P<0.01,P<0.01;P<0.05,P<0.05). 结论 KAI1的异常表达可能参与了大肠癌的发生、发展,并对肿瘤的分化、淋巴结转移的判断有一定指导意义。     

KAI1／CD82 mRNA和蛋白在鼻咽癌组织中的表达及意义

目的 探讨KAI1／CD82 mRNA和CD82蛋白在鼻咽癌组织中的表达及其与临床病理特征的关系。方法 采用免疫组化SP法检测70例鼻咽癌和30例正常鼻咽部组织中KAI1／CD82蛋白的表达情况;逆转录聚合酶链式反应（RT-PCR）检测28例鼻咽癌和15例正常鼻咽部新鲜组织中KAI1／CD82 mRNA的表达情况。分析KAI1／CD82 mRNA和CD82蛋白的表达与临床病理特征之间的关系。结果 KAI1／CD82 mRNA在鼻咽癌组织中的阳性表达率为42.9％（12／28）,低于正常鼻咽部组织中的73.3％（11／15）,差异无统计学意义（P＞0.05）;KAI1／CD82蛋白在鼻咽癌组织中的阳性表达率为44.3％（31／70）,低于正常鼻咽部组织中的700％（21／30）,差异有统计学意义（P＜0.05）。KAI1／CD82 mRNA和CD82蛋白在鼻咽癌组织中的表达与患者的性别、年龄、病理类型、T分期均无关（P＞0.05）,而与淋巴结转移有关。KAI1／CD82 mRNA和CD82蛋白在无淋巴结转移组中的阳性表达率分别为85.7％和68.4％,明显高于淋巴结转移组的28.6％和35.3％,差异均有统计学意义（P＜0.05）。KAI1／CD82 mRNA和CD82蛋白在N1、N2、N3亚组间表达率的差异无统计学意义（P＞0.05）。结论 KAI1／CD82 mRNA和CD82蛋白在鼻咽癌组织中表达下调,该基因可以抑制鼻咽癌发生、发展及淋巴结转移,有望作为鼻咽癌诊断和预后判定的一种有效分子标记物。     

脂质体介导KAI1基因转染对小细胞肺癌NCI-H446细胞株的抑制作用

 目的　探讨新抑癌基因KAI1对小细胞肺癌NCI H4 4 6细胞株抑制增殖和浸润转移的作用。方法　用脂质体介导的基因转染方法 ,借助真核质粒表达载体 (PCMV NEO XhoI) ,将抑癌基因KAI1转入小细胞肺癌NCI H4 4 6细胞中 ,经G4 18筛选 ,获得稳定表达的细胞克隆。观察NCI H4 4 6细胞的生长 ,MTT法检测细胞体外增殖能力 ,流式细胞仪进行细胞凋亡分析 ,间接免疫荧光染色结合流式细胞仪检测转染前后细胞CD82蛋白的表达。免疫组化测定Myc及MMP 1(基质金属蛋白酶 1)的表达 ,放射免疫测定LN(层黏蛋白 )表达。结果　脂质体 KAI1基因转染的小细胞肺癌细胞CD82表达增加 ,细胞增殖能力下降 ,凋亡增加 ,癌基因Myc ,MMP 1及LN表达下降。 结论　抑癌基因KAI1抑制小细胞肺癌NCI H4 4 6细胞株的增殖 ,降低Myc ,MMP 1及LN的表达。