%0 Journal Article
%T The bone morphogenetic protein antagonist gremlin 1 is overexpressed in human cancers and interacts with YWHAH protein
%A Hong Namkoong
%A Seung Shin
%A Hyun Kim
%A Seon-Ah Ha
%A Goang Cho
%A Soo Hur
%A Tae Kim
%A Jin Kim
%J BMC Cancer
%D 2006
%I BioMed Central
%R 10.1186/1471-2407-6-74
%X 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.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¨C80 and gremlin 1 binding site for YWHAH was found to be located between residues 1 to 67.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.The identification of molecular alterations in cancerous and pre-cancerous cells has provided insight into the role of oncogenes and tumor suppressor genes in tumor initiation and progression [1]. Oncogenes are derived from highly conserved proto-oncogenes that are altered by chromosomal point mutations, gene amplifications, or gene rearrangements
%U http://www.biomedcentral.com/1471-2407/6/74