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| Status |
Public on Oct 08, 2012 |
| Title |
TFPI alpha and beta regulate mRNAs involved in cancer biology and in the immune system |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Emerging evidences indicate a new role of TFPI in cancer biology. We recently reported that both isoforms of TFPI induced apoptosis and inhibited proliferation of cancer cells. The signaling pathway(s) mediating the effects of TFPI is, however, presently still unclear. Our goal was to further investigate the cellular processes affected by TFPI and to get insight into the molecular mechanisms involved in the effects of TFPI, using a global gene expression study approach. TFPIa or TFPIb cDNA were transfected into SK-BR-3 breast cancer cells for stable overexpression. Global mRNA and microRNA (miRNA) expressions were measured and functional annotation of the differentially expressed genes and miRNAs according to gene ontology terms was conducted. Selected results were validated using qRT-PCR and Western blot. Overexpression of TFPIa or TFPIb resulted in a 6.4- and 17-fold increase in TFPI protein levels, respectively. A total of 242 and 801 mRNA transcripts and 120 and 46 miRNAs were differentially expressed in cells overexpressing TFPIa or TFPIb, respectively. Overexpression of either isoform significantly affected the expression of genes involved in cell development (apoptosis, cell movement, migration, invasion, colony formation, growth, and adhesion) and immune response. Network analyses revealed biological interactions between these genes and implied that several of the genes may be involved in both processes. Functional cluster analyses indicated altered activity of the epidermal growth factor receptor (EGFR), small GTPases, and the NFkB and JAK/STAT cascades. Integrated mRNA-miRNA analyses showed that up to 46 and 252 genes differentially expressed in cells overexpressing TFPIa or TFPIb, respectively, may have been regulated by miRNAs. Overexpression of TFPI in breast cancer cells affected the expression of mRNAs and miRNAs involved in processes facilitating cancer cell growth and immunologic response, probably by signal transduction involving the EGFR pathway.
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| Overall design |
Total RNA was isolated from SK-BR-3 breast cancer cells stably transfected with TFPIalpha or TFPIbeta cDNA, or with an empty vector for control. RNA was obtained from three independent isolations, yielding three biological replicates of each of the three samples.
Mean expression data from cells overexpressing TFPIalpha or TFPIbeta were compared to mean data from cells transfected with an empty vector.
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| Contributor(s) |
Stavik B, Skretting G, Olstad OK, Sletten M, Vigeland MD, Sandset PM, Iversen N |
| Citation(s) |
23071754 |
| Submission date |
Jun 16, 2011 |
| Last update date |
Sep 19, 2019 |
| Contact name |
Nina Iversen |
| E-mail(s) |
nina.iversen@medisin.uio.no
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| Phone |
004723016647
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| Fax |
004723016629
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| Organization name |
Oslo University Hospital
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| Department |
Dept. of Medical Genetics
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| Street address |
Kirkeveien 166
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| City |
Oslo |
| ZIP/Postal code |
0407 |
| Country |
Norway |
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| Platforms (1) |
| GPL6244 |
[HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (9)
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| GSM743673 |
Overexpress TFPIalpha, biological rep. 1 |
| GSM743674 |
Overexpress TFPIalpha, biological rep. 2 |
| GSM743675 |
Overexpress TFPIalpha, biological rep. 3 |
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| Relations |
| BioProject |
PRJNA144065 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE30037_RAW.tar |
35.4 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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