Objective:This study aimed to investigate the role of receptor tyrosine kinase-like orphan receptor 2(ROR2)in triple-negative breast cancer(TNBC).Methods:ROR2 expression in primary TNBC and metastatic TNBC tissues was...Objective:This study aimed to investigate the role of receptor tyrosine kinase-like orphan receptor 2(ROR2)in triple-negative breast cancer(TNBC).Methods:ROR2 expression in primary TNBC and metastatic TNBC tissues was analyzed by immunohistochemical staining and PCR.ROR2 expression in TNBC cell lines was detected by PCR and Western blot analysis.The migration,invasion and chemosensitivity of TNBC cells with overexpression or knockdown of ROR2 were examined.Results:ROR2 expression was high in metastatic TNBC tissues.ROR2 knockdown suppressed the migration,invasion and chemoresistance of TNBC cells.ROR2 overexpression in MDA-MB-435 cells promoted the migration,invasion,and chemoresistance.Moreover,ROR2 knockdown in HC1599 and MDA-MB-435 adriamycin-resistant cells enhanced chemosensitivity to adriamycin.ROR2 could activate PI3K/AKT/mTOR signaling in TNBC cells.Conclusion:ROR2 is upregulated and promotes metastatic phenotypes of TNBC by activating PI3K/AKT/mTOR signaling.展开更多
AIM： To investigate the expression and clinical significance of Wnt member 5a （Wnt5a） and receptor tyrosine kinase-like orphan receptor 2 （Ror2） in hepatocellular carcinoma （HCC）.METHODS： In HCC tissues obtain...AIM： To investigate the expression and clinical significance of Wnt member 5a （Wnt5a） and receptor tyrosine kinase-like orphan receptor 2 （Ror2） in hepatocellular carcinoma （HCC）.METHODS： In HCC tissues obtained from 85 patients, the protein expressions of Wnt5a, Rot2, 13-catenin, and Ki-67 via immunohistochemical staining using the Envision Plus System. The antibody binding was visualized with 3, 3＇-diaminobenzidine tetrahydrochloride （DAB） before brief counterstaining with Mayer＇s hematoxylin. The degree of immunohistochemical staining was recorded using a semiquantitative and subjective grading system. The mRNA expression of Rot2 was examined by real time reverse transcription polymerase chain reaction, including nineteen of the 85 HCC and three normal liver tissues. The ratios of Ror2 to the housekeeping gene GAPDH represented the normalized relative levels of Ror2 expression. To determine the prognostic factor, the outcome of the 82 patients was determined by reviewing their medical charts. The overall and diseasefree survival rates were estimated using the Kaplan-Meier method and compared with the logrank test. The prognostic analysis was carried out with univariate and multivariate Cox regressions models.RESULTS： Compared to nontumorous （hepatitis or cirrhotic） tissues, Rot2 mRNA expression was clearly decreased in HCC. Rot2 and Wnt5a protein expressions in the majority of HCC patients （63% and 77%, respectively） was significantly less in tumor tissues, as compared to adjacent nontumorous tissues, and this reduction was correlated with increasing serum α-fetoprotein and tumor stage. In 68% （58/85） of the HCC cases, the expression of IB-catenin in tumor tissues was either downregulated in the cellular membrane, upregulated in the cytoplasm, or both. Survival analysis indicated that Wnt5a and Ror2 protein expressions could be regarded as independent prognostic factors for HCC; HCC patients with decreased Wnt5a or Ror2 protein expression had a poorer prognosis than those with elevated Wnt5a and Ror2 expression （P = 0.016, P = 0.007, respectively）.CONCLUSION： Wnt5a and Ror2 may serve as tumor suppressor genes in the development of HCC, and may serve as clinicopathologic biomarkers for prognosis in HCC patients.展开更多
Background The receptor tyrosine kinase-like orphan receptor 2 （ROR2） gene has been recently shown to play important roles in palatal development in animal models and resides in the chromosomal region linked to non ...Background The receptor tyrosine kinase-like orphan receptor 2 （ROR2） gene has been recently shown to play important roles in palatal development in animal models and resides in the chromosomal region linked to non syndromic cleft lip with or without cleft palate in humans.The aim of this study was to investigate the possible association between ROR2 gene and non-syndromic oral clefts.Methods Here we tested 38 eligible single-nucleotide polymorphisms （SNPs） in ROR2 gene in 297 non-syndromic cleft lip with or without cleft palate and in 82 non-syndromic cleft palate case parent trios recruited from Asia and Maryland.Family Based Association Test was used to test for deviation from Mendelian inheritance.Plink software was used to test potential parent of origin effect.Possible maternally mediated in utero effects were assessed using the TRlad Multi-Marker approach under an assumption of mating symmetry in the population.Results Significant evidence of linkage and association was shown for 3 SNPs （rs7858435,rs10820914 and rs3905385） among 57 Asian non-syndromic cleft palate trios in Family Based Association Tests.P values for these 3 SNPs equaled to 0.000068,0.000115 and 0.000464 respectively which were all less than the significance level （0.05/38=0.0013） adjusted by strict Bonferroni correction.Relevant odds ratios for the risk allele were 3.42 （1.80-6.50）,3.45 （1.75-6.67） and 2.94 （1.56-5.56）,respectively.Statistical evidence of linkage and association was not shown for study groups other than non-syndromic cleft palate.Neither evidence for parent-of-origin nor maternal genotypic effect was shown for any of the ROR2 markers in our analysis for all study groups.Conclusion Our results provided evidence of linkage and association between the ROR2 gene and a gene controlling risk to non-syndromic cleft palate.展开更多
基金supported by Medical and Health Research Project of Nanjing Health Science and Technology Development Special Fund(ZKX21040).
文摘Objective:This study aimed to investigate the role of receptor tyrosine kinase-like orphan receptor 2(ROR2)in triple-negative breast cancer(TNBC).Methods:ROR2 expression in primary TNBC and metastatic TNBC tissues was analyzed by immunohistochemical staining and PCR.ROR2 expression in TNBC cell lines was detected by PCR and Western blot analysis.The migration,invasion and chemosensitivity of TNBC cells with overexpression or knockdown of ROR2 were examined.Results:ROR2 expression was high in metastatic TNBC tissues.ROR2 knockdown suppressed the migration,invasion and chemoresistance of TNBC cells.ROR2 overexpression in MDA-MB-435 cells promoted the migration,invasion,and chemoresistance.Moreover,ROR2 knockdown in HC1599 and MDA-MB-435 adriamycin-resistant cells enhanced chemosensitivity to adriamycin.ROR2 could activate PI3K/AKT/mTOR signaling in TNBC cells.Conclusion:ROR2 is upregulated and promotes metastatic phenotypes of TNBC by activating PI3K/AKT/mTOR signaling.
基金Supported by The fund of Nature Science Foundation of Shandong Province,No.ZR2009CM041
文摘AIM： To investigate the expression and clinical significance of Wnt member 5a （Wnt5a） and receptor tyrosine kinase-like orphan receptor 2 （Ror2） in hepatocellular carcinoma （HCC）.METHODS： In HCC tissues obtained from 85 patients, the protein expressions of Wnt5a, Rot2, 13-catenin, and Ki-67 via immunohistochemical staining using the Envision Plus System. The antibody binding was visualized with 3, 3＇-diaminobenzidine tetrahydrochloride （DAB） before brief counterstaining with Mayer＇s hematoxylin. The degree of immunohistochemical staining was recorded using a semiquantitative and subjective grading system. The mRNA expression of Rot2 was examined by real time reverse transcription polymerase chain reaction, including nineteen of the 85 HCC and three normal liver tissues. The ratios of Ror2 to the housekeeping gene GAPDH represented the normalized relative levels of Ror2 expression. To determine the prognostic factor, the outcome of the 82 patients was determined by reviewing their medical charts. The overall and diseasefree survival rates were estimated using the Kaplan-Meier method and compared with the logrank test. The prognostic analysis was carried out with univariate and multivariate Cox regressions models.RESULTS： Compared to nontumorous （hepatitis or cirrhotic） tissues, Rot2 mRNA expression was clearly decreased in HCC. Rot2 and Wnt5a protein expressions in the majority of HCC patients （63% and 77%, respectively） was significantly less in tumor tissues, as compared to adjacent nontumorous tissues, and this reduction was correlated with increasing serum α-fetoprotein and tumor stage. In 68% （58/85） of the HCC cases, the expression of IB-catenin in tumor tissues was either downregulated in the cellular membrane, upregulated in the cytoplasm, or both. Survival analysis indicated that Wnt5a and Ror2 protein expressions could be regarded as independent prognostic factors for HCC; HCC patients with decreased Wnt5a or Ror2 protein expression had a poorer prognosis than those with elevated Wnt5a and Ror2 expression （P = 0.016, P = 0.007, respectively）.CONCLUSION： Wnt5a and Ror2 may serve as tumor suppressor genes in the development of HCC, and may serve as clinicopathologic biomarkers for prognosis in HCC patients.
文摘Background The receptor tyrosine kinase-like orphan receptor 2 （ROR2） gene has been recently shown to play important roles in palatal development in animal models and resides in the chromosomal region linked to non syndromic cleft lip with or without cleft palate in humans.The aim of this study was to investigate the possible association between ROR2 gene and non-syndromic oral clefts.Methods Here we tested 38 eligible single-nucleotide polymorphisms （SNPs） in ROR2 gene in 297 non-syndromic cleft lip with or without cleft palate and in 82 non-syndromic cleft palate case parent trios recruited from Asia and Maryland.Family Based Association Test was used to test for deviation from Mendelian inheritance.Plink software was used to test potential parent of origin effect.Possible maternally mediated in utero effects were assessed using the TRlad Multi-Marker approach under an assumption of mating symmetry in the population.Results Significant evidence of linkage and association was shown for 3 SNPs （rs7858435,rs10820914 and rs3905385） among 57 Asian non-syndromic cleft palate trios in Family Based Association Tests.P values for these 3 SNPs equaled to 0.000068,0.000115 and 0.000464 respectively which were all less than the significance level （0.05/38=0.0013） adjusted by strict Bonferroni correction.Relevant odds ratios for the risk allele were 3.42 （1.80-6.50）,3.45 （1.75-6.67） and 2.94 （1.56-5.56）,respectively.Statistical evidence of linkage and association was not shown for study groups other than non-syndromic cleft palate.Neither evidence for parent-of-origin nor maternal genotypic effect was shown for any of the ROR2 markers in our analysis for all study groups.Conclusion Our results provided evidence of linkage and association between the ROR2 gene and a gene controlling risk to non-syndromic cleft palate.
