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Human chorionic gonadotropin β (β-hCG) has been implicated in breast tumorigenesis. However, the role of this hormone is highly controversial as certain studies suggest it has anti-tumor properties while others have found it to be pro-tumorigenic. To unveil the truth, we have analyzed the expression of β-hCG in breast cancer. We identified for the first time that β-hCG expression is linked to BRCA1 status and its overexpression is seen in BRCA1 mutated breast cancer cells, BRCA1 conditional knockout mouse breast cancer tissues and BRCA1 floxed basal cell carcinoma (BCC) tissues. An analysis of three large, transcriptomic data sets from TCGA (The Cancer Genome Atlas) expression profile confirmed the inverse correlation between BRCA1 and β-hCG in human breast cancer. Using ChIP and luciferase assays, we also demonstrated that the cancer cells with wild-type but not mutant BRCA1 directly repress the expression of β-hCG by binding to its promoter. Further, β-hCG promotes migration and invasion predominantly in BRCA1 mutant breast cancer cells. Interestingly, stable overexpression of β-hCG in BRCA1 mutant but not wild-type breast cancer cells results in the formation of spheres even on monolayer cultures. The cells of these spheres show high expression of both EMT and stem cell markers. Since β-hCG belongs to a cysteine knot family of proteins like TGFβ and TGFβ signaling is deregulated in BRCA1 defective tumors, we checked whether β-hCG can mediate signaling through TGFβRII in BRCA1 mutated cells. We found for the first time that β-hCG can bind and phosphorylate TGFβRII, irrespective of LHCGR status and induce proliferation in BRCA1 defective cells. Our results confirmed that there exists a transcriptional regulation of BRCA1 on β-hCG and BRCA1 mutation promotes β-hCG mediated tumorigenesis through TGFβRII signaling. Thus inhibiting β-hCG-TGFβRII could prove an effective treatment strategy for BRCA1 mutated tumors.
Pubmed ID: 28869585 RIS Download
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View all literature mentionsGlobal nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.
View all literature mentionsNon-profit plasmid repository dedicated to helping scientists around the world share high-quality plasmids. Facilitates archiving and distributing DNA-based research reagents and associated data to scientists worldwide. Repository contains over 65,000 plasmids, including special collections on CRISPR, fluorescent proteins, and ready-to-use viral preparations. There is no cost for scientists to deposit plasmids, which saves time and money associated with shipping plasmids themselves. All plasmids are fully sequenced for validation and sequencing data is openly available. We handle the appropriate Material Transfer Agreements (MTA) with institutions, facilitating open exchange and offering intellectual property and liability protection for depositing scientists. Furthermore, we curate free educational resources for the scientific community including a blog, eBooks, video protocols, and detailed molecular biology resources.
View all literature mentionsProject exploring the spectrum of genomic changes involved in more than 20 types of human cancer that provides a platform for researchers to search, download, and analyze data sets generated. As a pilot project it confirmed that an atlas of changes could be created for specific cancer types. It also showed that a national network of research and technology teams working on distinct but related projects could pool the results of their efforts, create an economy of scale and develop an infrastructure for making the data publicly accessible. Its success committed resources to collect and characterize more than 20 additional tumor types. Components of the TCGA Research Network: * Biospecimen Core Resource (BCR); Tissue samples are carefully cataloged, processed, checked for quality and stored, complete with important medical information about the patient. * Genome Characterization Centers (GCCs); Several technologies will be used to analyze genomic changes involved in cancer. The genomic changes that are identified will be further studied by the Genome Sequencing Centers. * Genome Sequencing Centers (GSCs); High-throughput Genome Sequencing Centers will identify the changes in DNA sequences that are associated with specific types of cancer. * Proteome Characterization Centers (PCCs); The centers, a component of NCI's Clinical Proteomic Tumor Analysis Consortium, will ascertain and analyze the total proteomic content of a subset of TCGA samples. * Data Coordinating Center (DCC); The information that is generated by TCGA will be centrally managed at the DCC and entered into the TCGA Data Portal and Cancer Genomics Hub as it becomes available. Centralization of data facilitates data transfer between the network and the research community, and makes data analysis more efficient. The DCC manages the TCGA Data Portal. * Cancer Genomics Hub (CGHub); Lower level sequence data will be deposited into a secure repository. This database stores cancer genome sequences and alignments. * Genome Data Analysis Centers (GDACs) - Immense amounts of data from array and second-generation sequencing technologies must be integrated across thousands of samples. These centers will provide novel informatics tools to the entire research community to facilitate broader use of TCGA data. TCGA is actively developing a network of collaborators who are able to provide samples that are collected retrospectively (tissues that had already been collected and stored) or prospectively (tissues that will be collected in the future).
View all literature mentionsA portal that provides visualization, analysis and download of large-scale cancer genomics data sets.
View all literature mentionsOncomine Research Platform is a partially-commercial suite of products for online cancer gene expression analysis dedicated to the academic and non-profit research community. Oncomine combines a rapidly growing compendium of 20,000+ cancer transcriptome profiles with a sophisticated analysis engine and a powerful web application for data-mining and visualization. Oncomine facilitates rapid and reliable biomarker and therapeutic target discovery, validation and prioritization. Oncomine was developed by physicians, scientists, and software engineers at the University of Michigan and is now fully supported for the academic and non-profit research community by Compendia Bioscience.
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View all literature mentionsCell line DU145 is a Cancer cell line with a species of origin Homo sapiens (Human)
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