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Purpose To investigate the expression and significance of type L amino acid transporter 1 (LAT1 ) and phosphorylated s6 ribosomal protein (p-s6) in breast cancer tissues and their correlation. Methods LAT1 protein and p-s6 protein were detected by immunohistochemical EnVision two step method in 178 cases of breast cancer and 78 cases of benign breast lesion, and the relationship between the expression and clinicopathological parameters was analyzed. Results The positive rate of LAT1 in breast cancer was 36.5％, which was significantly higher than that of breast benign lesion tissues (23.1 ％, P＜ 0.05 ), the positive rate of p-s6 in breast cancer tissues was33.2％, which was significantly higher than that of breast benign lesion tissues (12.8％, P＜0.05). There was a positive correlation between the expression of LAT1 protein and p-s6 protein in breast cancer tissues (r = 0.345, P＜ 0.05). The expression of LAT1 protein in breast cancer was correlated with tumor diameter, axillary lymph node metastasis, TNM staging and HER-2 level (P＜ 0.05), but not associated with the patient's age, histological grade, ER, and PR levels (P＞ 0.05). The expression of p-s6 protein was related to axillary lymph node metastasis, TNM staging, age and ER level (P＜ 0.05), but not associated with tumor diameter, histological grade, PR and HER-2 levels (P＞ 0.05 ). Multivariate analysis showed that the expres sion of LAT1 protein was related to tumor diameter and expression level of HER-2. The expression of p-s6 protein was related to axillary lymph node metastasis. Conclusion The expression of LAT1 protein and p-s6 protein in breast cancer is up-regulated, and the expression of these two proteins is positively related, which implying that LAT1 and p-s6 might play a synergistic role in the development and progression of breast cancer.
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OBJECTIVE: ASCT2 and LAT1 are aminoacid transporters involved in glutamine transport and play a role in tumor growth. Previous studies have shown an association of ASCT2 to cell proliferation through the mechanistic Target of Rapamycin (mTOR) translational machinery; LAT1 has been shown as a prognostic marker due to its relation to tumor invasion, microscopic vascular invasion and metastasis. This study analyzed the gene expression of ASCT2 and LAT1 in astrocytomas of different grades and how this correlates to clinical outcome in glioblastoma patients. METHOD: This is an observational study with ASCT2 and LAT1 mRNA expression analysis in 153 samples of human astrocytomas, distributed in different World Health Organization (WHO) grades of malignancy (23 at grade I or pilocytic astrocytoma, 26 at grade II or low-grade astrocytoma, 18 at grade III or anaplastic astrocytoma, 86 at grade IV astrocytoma or glioblastoma (AGIV or GBM)); these were compared to 22 non-neoplastic brain samples. RESULTS: Significant hyperexpression of both genes was observed particularly in malignant astrocytomas (GIII & GBM). Moreover, LAT1 hyperexpression impacted negatively in the overall survival in a subset of GBM patients. CONCLUSION: LAT1 is more expressed in higher grade astrocytomas. It leads to a poorer prognosis among GBM patients and may be a potential therapeutical target.
OBJETIVO: ASCT2 e LAT1 são transportadores de aminoácidos envolvidos no transporte de glutamina e desempenham um papel no crescimento tumoral. Estudos prévios mostraram uma associação de ASCT2 com proliferação celular através da maquinaria de tradução do mTOR; tem sido mostrado que o LAT1 é um marcador prognóstico devido à sua relação com invasão tumoral, invasão vascular microscópica e metástase. Este estudo analisou a expressão gênica de ASCT2 e LAT1 em astrocitomas de diferentes graus e sua correlação com desfecho clínico em pacientes com glioblastoma. METODO: Este é um estudo observacional com análise de expressão de RNAm de ASCT2 e LAT1 em 153 amostras de astrocitomas humanos, distribuídas em diferentes graus de malignidade segundo a OMS (23 astrocitomas de grau I ou astrocitoma pilocítico, 26 de astrocitoma de grau II ou astrocitoma de baixo grau, 18 de astrocitoma de grau III ou astrocitoma anaplásico, 86 de astrocitoma de grau IV ou glioblastoma (AGIV ou GBM); estes foram comparados com 22 amostras cerebrais não neoplásicas. RESULTADOS: Foi observada uma hiperexpressão de ambos os genes, particularmente nos astrocitomas malignos (GIII & GBM). Além disso, a hiperexpressão LAT1 impactou negativamente na sobrevida global em um grupo de pacientes com GBM. CONCLUSÃO: LAT1 é mais expresso em astrocitomas de grau maior. Isso leva a um pior prognóstico entre os pacientes com GBM e pode ser um potencial alvo terapêutico.
Subject(s)
Humans , Astrocytoma , Gene Expression , Glioblastoma/pathology , Large Neutral Amino Acid-Transporter 1/analysis , GlutamineABSTRACT
Objective:To observe the expression of Ki-67,P53 and LAT1 in tissues of esophageal squamous cell carcinoma and precancerous lesions and to investigate its clinical significance.Methods: Immunohistochemical method was used to detect the expressions of Ki-67,P53 and LAT1 in tissues from 20 cases of normal esophageal mucosa,68 cases of precancerous lesions including 21 cases of mild atypical hyperplasia,22 cases of atypical hyperplasia,25 cases of severe atypical hyperplasia and cancer tissues from 34 esophageal cancer patients.The relationship between the expression of the three in esophageal carcinoma was analysed.Results: Re-spectively,the positive expression rate of Ki-67 in normal esophageal mucosa, mild atypical hyperplasia, moderate dysplasia, severe dysplasia and carcinoma was 0%( 0/20 ) , 23.8%( 5/21 ) , 40.9%( 9/22 ) , 76.0%( 19/25 ) , 82.4%( 28/34 ) and the positive expression rate of P53 was 0%(0/20),14.3%(3/21),31.8%(7/22),48.0%(12/25),67.6%(23/34) and the positive expression rate of LAT1 was 0%( 0/20 ) , 19.0%( 4/21 ) , 36.4%( 8/22 ) , 52.0%( 13/25 ) , 76.5%( 26/34 ).The rank correlation analysis showed that the positive expression of Ki-67,P53 and LAT1 were significantly correlated with histological grade(r=0.626,0.427, 0.586,P<0.01) and the expression of Ki-67,P53 was positively correlated with LAT1 in esophageal carcinoma tissues(r=0.428, 0.596,P<0.01).Conclusion:Abnormal expression of Ki-67,P53,LAT1 protein was significant related to carcinogenesis of esophageal cancer and the combined detection of the three has important clinical significance.
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Objective:Glutamine is the main oxidative fuel of the enterocyte which enters the enterocyte primarily via amino acid transporters.The aim of the test was to study the distributions and functions of glutamine transporters in IEC-6 cell line.Methods:The rat intestinal epithelial cell line(IEC-6) was incubated in vitro.The mRNA expression of different glutamine transporters,protein expression of system ASCT2,and the [3H]-L-glutamine uptake were measured.Results:The mRNA of system ASCT2,SN1,ATA1,LAT1,LAT2 was expressed and the protein expression of ASCT2 was also validated in IEC-6.In Na+-containing buffer,the velocity of Na+-dependent glutamine uptake was(164.07?37.94) fmol/(mg protein?10min).In Na+-free buffer,the velocity of glutamine uptake was(58.71?10.51)fmol/(mg protein?10min).With the saturate dosage of MeAIB,the velocity of glutamine uptake was(81.02 ?19.59) fmol/(mg protein?10min).Conclusion:There may be five kinds of glutamine transporters(ASCT2,SN1,ATA1,LAT1,and LAT2) in IEC-6 cell.The Na+-dependent transporter was the major contributor(64.22%) to glutamine total uptake in IEC-6.The contributions of system A and the remainder were 50.62% and 13.60%,respectively.The Na+-independent transporter was the lesser contributor(35.78%).