Lysosome-associated Protein Transmembrane 4 Beta Gene Research Articles

LAPTM4B gene polymorphism augments the risk of cancer: Evidence from an updated meta-analysis.

Lysosome‐associated protein transmembrane‐4 beta (LAPTM4B) has two alleles named as LAPTM4B*1 and LAPTM4B*2 (GenBank No. AY219176 and AY219177). Allele *1 has a single copy of a 19‐bp sequence in the 5` untranslated region (5`UTR), but allele *2 contains tandem repeats of 19‐bp sequence.1 LAPTM4B gene is located on long chromosome 8 (8q22.1) and contains seven exons that encodes two isoforms of tetratransmembrane proteins, LAPTM4B‐24 and LAPTM4B‐35, with molecular weights of 25 kDa and 35 kDa respectively. The LAPTM4B‐35′s primary structure is formed by 317 amino acid residues, and LAPTM4B‐24 comprised 226 amino acids. LAPTM4B, an integral membrane protein, contains several lysosomal‐targeting motifs at the C terminus and colocalizes with late endosomal and lysosomal markers. LAPTM4B is a proto‐oncogene, which becomes up‐regulated in various cancers. Preceding studies have examined the possible link between LAPTM4B polymorphism and susceptibility to several cancers,1-26 but the findings are still inconsistent. Hence, the present meta‐analysis was designed to investigate the impact of LAPTM4B polymorphism on risk of cancer.

LAPTM4B Down Regulation Inhibits the Proliferation, Invasion and Angiogenesis of HeLa Cells In Vitro

Background/Aims: LAPTM4B (lysosome-associated protein transmembrane 4 beta) is a novel oncogene with important functions in aggressive human carcinomas, including cervical cancer. However, the specific functions and internal molecular mechanisms associated with this gene in the context of cervical cancer remain unclear. Methods: In this study, we explored the effects and mechanisms of LAPTM4B on tumor growth, metastasis and angiogenesis in vitro by depletion of LAPTM4B in Hela cell. RNA interference was used to induce down regulation of LAPTM4B gene expression in Hela cells. The motility, migration potential, and proliferation of the Hela cells were measured by flow cytometry, Transwell migration assays, wound healing assays, and Cell Counting Kit-8 assays. In addition, the cell cycle analysis utilized fluorescence-activated cell sorting. Results: In this study, RNAi-mediated LAPTM4B knockdown inhibited cell growth and angiogenesis. In vitro, HeLa cells with down regulated LAPTM4B also exhibited decreased migration and invasion activity as well as significantly reduced CDK12, HIF-1α, MMP-2, MMP-9 and VEGF expression. LAPTM4B blockade significantly decreased cord lengths and branch points in a tube formation assay. Conclusions: These results suggested that LAPTM4B inactivation could be a novel therapeutic target for cervical cancer.

Association between LAPTM4B gene polymorphism and breast cancer susceptibility in an Iranian population.

Lysosome associated protein transmembrane 4beta (LAPTM4B) contribute to the risk of numerous cancers. The present study focused on the possible association between LAPTM4B polymorphism and the risk of breast cancer (BC) in an Iranian population in southeast Iran. This case control study includes 311 BC patients and 225 healthy women. Genomic DNA was extracted from the whole blood by salting out method and LAPTM4B genotype was investigated using polymerase chain reaction. Our findings showed that LAPTM4B genotype was not associated with the risk of BC in any inheritance model tested. The minor allele frequency in case and control group was 0.297 and 0.278, respectively. The minor allele (LAPTM4B*2) was not associated with BC risk in comparison with LAPTM4B*1 allele (odds ratio 1.10, 95 % confidence intervals 0.84-1.44, p = 0.495). Moreover, LAPTM4B polymorphism was not associated with clinical and pathological characteristics in the patient group. In conclusion, the findings of our study suggested that the polymorphism of LAPTM4B gene was not associated with susceptibility to BC and clinicopathological characteristics in an Iranian population.

Association of LAPTM4B gene polymorphism with nasopharyngeal carcinoma susceptibility in a Chinese population

Lysosome-associated protein transmembrane-4 beta (LAPTM4B) is a novel cancer-related gene. It has two alleles designated LAPTM4B 1 and LAPTM4B 2. Previous studies have revealed that LAPTM4B polymorphisms contribute to the risk of many cancers. The aim of this study was to investigate the association between different LAPTM4B alleles and the risk of nasopharyngeal carcinoma (NPC), one of the most common cancers in southern China. Using polymerase chain reaction (PCR) in a case-control study, we detected the LAPTM4B genotype in peripheral blood samples from 134 patients with NPC and 327 control subjects. The chi-square test was used to analyze differences of categorical variables and Hardy-Weinberg equilibrium. Odds ratios and 95 % CI were computed using an unconditional logistic regression model. The frequency of allele 2 was 26.87 % in the NPC group, which was not significantly different from that of the control group (27.98 %, P = 0.867). Using the LAPTM4B 1/1 genotype as a reference, we found that the 1/2, 2/2 and 1/2 + 2/2 genotype were also not associated with the risk of NPC. No association was observed between LAPTM4B gene polymorphisms and the risk of NPC adjusted by gender and age. The results of our study indicated that the polymorphism of LAPTM4B gene did not influence the susceptibility of NPC in the Chinese population. Large-scale studies are needed to confirm our findings.

LAPTM4B gene polymorphism and endometrial carcinoma risk and prognosis

A novel gene called LAPTM4B (lysosome-associated protein transmembrane 4 beta) plays several crucial roles in carcinogenesis. In this case-control study, we investigated the relationship between LAPTM4B gene polymorphism and susceptibility to endometrial carcinoma (EC). In an adjusted multivariate logistic regression analyses, subjects with the LAPTM4B*1/2 and *2/2 genotypes respectively exhibited 1.572-fold (95% confidence interval (CI) = 1.041–2.375) and 2.335-fold (95% CI = 1.365–3.995) increases in the risk of developing EC relative to those carrying LAPTM4B*1/1. Patients with LAPTM4B *2 had both significantly shorter overall survival (OS) and shorter disease-free survival (DFS) (both p < 0.001). Multivariate analysis showed that LAPTM4B genotype is an independent prognostic factor for OS and DFS (both p < 0.001). These results suggest that LAPTM4B polymorphisms might play an important role in the aetiology of EC.

Relationship between LAPTM4B gene polymorphism and susceptibility of gastric cancer

A novel gene called LAPTM4B (lysosome-associated protein transmembrane 4beta) was mapped to 8q22, and contains seven exons. The 2.25-kb messenger RNA of the gene encodes a putative lysosome-associated protein with four transmembrane regions. There are two alleles of the gene, named as LAPTM4B*1 and LAPTM4B*2. Allele *1 differs from allele *2 in that it contains only one copy of a 19-bp sequence in the 5' untranslated region (UTR), whereas this sequence is duplicated and tandemly arranged in allele *2. Studies showed that the allelic variation of LAPTM4B was associated with the genetic susceptibility of hepatocellular carcinoma but not with that of esophageal squamous cell carcinoma. This study was designed to investigate the possible association between the allelic variation of LAPTM4B and the genetic susceptibility of gastric cancer. The genotype of LAPTM4B was analyzed in 350 unrelated healthy adult individuals and 214 patients with gastric cancer by utilizing polymerase chain reaction based on specific primers. The genotypic distribution of LAPTM4B was analyzed by chi(2) test. The allelic frequencies of the *2 were 33.88% and 24.14% in the gastric cancer group and the healthy control group, respectively, which was significantly different between the two groups (P < 0.001). There was a significant difference in the overall genotypic distribution between the patients and the controls (P = 0.023). The risk of suffering from gastric cancer was increased 1.819 times in the individuals of the *1/2 genotype [95% confidence interval (CI) 1.273-2.601] and 2.387 times in the individuals of the *2/2 genotype of LAPTM4B (95% CI 1.195-4.767) compared with the *1/1 genotype. No association between the genotypic distribution of LAPTM4B and the clinical information on patients of gastric cancer such as age, pathological type, differentiation classification of TNM, and infection of hepatitis B virus was shown. This study indicated that allele *2 of LAPTM4B might be the risk factor of gastric cancer, which could be associated with genetic susceptibility of gastric cancer.

Relationship between LAPTM4B gene polymorphism and susceptibility of lung cancer

It has been proved that lysosome-associated protein transmembrane 4 beta (LAPTM4B) plays an important role in tumorigenesis, the *2/*2 genotype of LAPTM4B was closely related to liver cancer susceptibity. The aim of this study is to investigate the possible association between the allelic variation of LAPTM4B and the genetic susceptibility of lung cancer. The genotype of LAPTM4B was detected in 131 patients with lung cancer and 104 unrelated healthy adult individuals as control by polymerase chain reaction based on special primers. The genotypic distribution of LAPTM4B was analyzed by Chi-square test. The allelic frequencies of the *1 and *2 were 74.8% and 25.2% in the lung cancer group and 72.1% and 27.9% in the healthy control group respectively, but no significant difference was observed between the two groups (Chi-square=0.433, P=0.510). The genotypic distribution of the *1/*1,*1/*2 and *2/*2 were 53.4%, 42.7% and 3.8% in the lung cancer group, 54.8%, 34.6% and 10.6% in the healthy control group respectively, there was no significant difference between the two groups (Chi-square=4.89, P=0.087). No remarkable association was observed between the genotypic distribution of LAPTM4B and the clinical information in the patients with lung cancer, including pathological type and TNM staging. The results suggest that the allele of LAPTM4B is not closely associated with genetic susceptibility of lung cancer.