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| Status |
Public on May 15, 2024 |
| Title |
SIVA mutation, a candidate metastasis gene identified from clonally related bilateral breast cancers, promotes breast cancer cell aggressiveness in vitro and in vivo |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Our purpose is to identify candidate genes involved in the early steps of breast cancer metastasis and examine their pro-invasive functions both in vitro and in vivo. A percentage of bilateral breast cancers were clonally related based on copy number variation profiling. Whole exome sequencing and comparative sequence analysis revealed that a limited number of somatic mutations were acquired in this “breast to breast” metastasis. These mutations might promote breast cancer distant spread. The pro-invasive functions of a candidate metastasis gene were assessed in vitro by its abilities to promote proliferation, migration and invasion and in vivo as tumor xenografts in immunocompromised mice or a syngeneic orthotopic mouse breast cancer model. RNAseq analysis was performed to probe the transcription programs modulated by this candidate metastasis gene. SIVA1-D160N was one somatic mutation acquired in the breast to breast metastasis. Over-expression of SIVA1-D160N promoted migration and invasion of human MB-MDA-231 breast cancer cells in vitro, consistent with a dominant negative interfering function. When introduced via tail vein injection, 231 cells over-expressing SIVA1-D160N displayed enhanced distant spread on IVIS imaging. Over-expression of SIVA1-D160N promoted anchorage independent growth of mouse 4T1 breast cancer cells in vitro. When introduced orthotopically via mammary fat pad injection in syngeneic Balb/c mice, over-expression of SIVA1-D160N in 4T1 cells increased mammary gland tumor growth as well as liver metastasis. We conclude clonally related bilateral breast cancers represent a novel system to investigate metastasis and revealed a role of SIVA1-D160N in breast cancer metastasis.
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| Overall design |
Differential gene expression analysis and pathway enrichment analysis of OVCAR8, SKOV3, HCC1954, and MDA-MB-231 parental cell lines as compared to their SIVA1-WT or SIVA1-D160N transformed counterparts.
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| Contributor(s) |
Vermehren-Schmaedick A, Luoh S, Spellman P, Sears R, Wang X, Ramsey E, Chiotti K, Wagoner W, Peto M |
| Citation(s) |
38722955 |
| Submission date |
Sep 01, 2023 |
| Last update date |
May 15, 2024 |
| Contact name |
Shiuh-Wen Luoh |
| E-mail(s) |
luohs@ohsu.edu
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| Organization name |
Oregon Health & Science University
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| Department |
MMG
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| Street address |
3181 SW Sam Jackson Park Rd
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| City |
Portland |
| State/province |
OR |
| ZIP/Postal code |
97239 |
| Country |
USA |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA1011994 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE242210_cpm_values.tsv.gz |
1.6 Mb |
(ftp)(http) |
TSV |
| GSE242210_rawcounts.tsv.gz |
936.6 Kb |
(ftp)(http) |
TSV |
SRA Run Selector |
| Raw data are available in SRA |
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