The bone morphogenetic protein antagonist gremlin 1 is overexpressed in human cancers and interacts with YWHAH protein
The bone morphogenetic protein antagonist gremlin 1 is overexpressed in human cancers and interacts with YWHAH protein
Abstract Background Basic studies of oncogenesis have demonstrated that either the elevated production of particular oncogene proteins or the occurrence of qualitative abnormalities in oncogenes can contribute to neoplastic cellular transformation. The purpose of our study was to identify an unique gene that shows cancer-associated expression, and characterizes its function related to human carcinogenesis. Methods We used the differential display (DD) RT-PCR method using normal cervical, cervical cancer, metastatic cervical tissues, and cervical cancer cell lines to identify genes overexpressed in cervical cancers and identified gremlin 1 which was overexpressed in cervical cancers. We determined expression levels of gremlin 1 using Northern blot analysis and immunohistochemical study in various types of human normal and cancer tissues. To understand the tumorigenesis pathway of identified gremlin 1 protein, we performed a yeast two-hybrid screen, GST pull down assay, and immunoprecipitation to identify gremlin 1 interacting proteins. Results DDRT-PCR analysis revealed that gremlin 1 was overexpressed in uterine cervical cancer. We also identified a human gremlin 1 that was overexpressed in various human tumors including carcinomas of the lung, ovary, kidney, breast, colon, pancreas, and sarcoma. PIG-2-transfected HEK 293 cells exhibited growth stimulation and increased telomerase activity. Gremlin 1 interacted with homo sapiens tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, eta polypeptide (14-3-3 eta; YWHAH). YWHAH protein binding site for gremlin 1 was located between residues 61–80 and gremlin 1 binding site for YWHAH was found to be located between residues 1 to 67. Conclusion Gremlin 1 may play an oncogenic role especially in carcinomas of the uterine cervix, lung, ovary, kidney, breast, colon, pancreas, and sarcoma. Over-expressed gremlin 1 functions by interaction with YWHAH. Therefore, Gremlin 1 and its binding protein YWHAH could be good targets for developing diagnostic and therapeutic strategies against human cancers.
- Catholic University of Korea Korea (Republic of)
Models, Molecular, Cancer Research, Blotting, Western, Models, Biological, Cell Line, Protein Interaction Mapping, Genetics, Humans, Immunoprecipitation, Tissue Distribution, Telomerase, RC254-282, Cell Proliferation, Glutathione Transferase, Reverse Transcriptase Polymerase Chain Reaction, Gene Expression Profiling, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Blotting, Northern, Immunohistochemistry, Gene Expression Regulation, Neoplastic, Cell Transformation, Neoplastic, Oncology, 14-3-3 Proteins, Intercellular Signaling Peptides and Proteins, Research Article, Protein Binding
Models, Molecular, Cancer Research, Blotting, Western, Models, Biological, Cell Line, Protein Interaction Mapping, Genetics, Humans, Immunoprecipitation, Tissue Distribution, Telomerase, RC254-282, Cell Proliferation, Glutathione Transferase, Reverse Transcriptase Polymerase Chain Reaction, Gene Expression Profiling, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Blotting, Northern, Immunohistochemistry, Gene Expression Regulation, Neoplastic, Cell Transformation, Neoplastic, Oncology, 14-3-3 Proteins, Intercellular Signaling Peptides and Proteins, Research Article, Protein Binding
7 Research products, page 1 of 1
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).104 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
