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Embryonic Morphogen Nodal Promotes Breast Cancer Growth and Progression
- Source :
- Paediatrics Publications, PLoS ONE, Vol 7, Iss 11, p e48237 (2012), PLoS ONE
- Publication Year :
- 2012
- Publisher :
- Public Library of Science (PLoS), 2012.
-
Abstract
- Breast cancers expressing human embryonic stem cell (hESC)-associated genes are more likely to progress than well-differentiated cancers and are thus associated with poor patient prognosis. Elevated proliferation and evasion of growth control are similarly associated with disease progression, and are classical hallmarks of cancer. In the current study we demonstrate that the hESC-associated factor Nodal promotes breast cancer growth. Specifically, we show that Nodal is elevated in aggressive MDA-MB-231, MDA-MB-468 and Hs578t human breast cancer cell lines, compared to poorly aggressive MCF-7 and T47D breast cancer cell lines. Nodal knockdown in aggressive breast cancer cells via shRNA reduces tumour incidence and significantly blunts tumour growth at primary sites. In vitro, using Trypan Blue exclusion assays, Western blot analysis of phosphorylated histone H3 and cleaved caspase-9, and real time RT-PCR analysis of BAX and BCL2 gene expression, we demonstrate that Nodal promotes expansion of breast cancer cells, likely via a combinatorial mechanism involving increased proliferation and decreased apopotosis. In an experimental model of metastasis using beta-glucuronidase (GUSB)-deficient NOD/SCID/mucopolysaccharidosis type VII (MPSVII) mice, we show that although Nodal is not required for the formation of small (
- Subjects :
- Pathology
Lung Neoplasms
Gene Expression
lcsh:Medicine
Apoptosis
Mice, SCID
Metastasis
Mice
Prostate cancer
0302 clinical medicine
Mice, Inbred NOD
Molecular Cell Biology
Basic Cancer Research
RNA, Small Interfering
lcsh:Science
skin and connective tissue diseases
0303 health sciences
Gene knockdown
Multidisciplinary
Stem Cells
Obstetrics and Gynecology
Cell Differentiation
Neoplasm Proteins
Tumor Burden
3. Good health
Oncology
Neoplasm Micrometastasis
Gene Knockdown Techniques
030220 oncology & carcinogenesis
Disease Progression
Medicine
Intercellular Signaling Peptides and Proteins
Female
Cellular Types
Research Article
medicine.medical_specialty
Nodal Protein
Mice, Nude
Breast Neoplasms
Biology
GPI-Linked Proteins
Cell Growth
03 medical and health sciences
Breast cancer
Cell Line, Tumor
Breast Cancer
medicine
Animals
Humans
Embryonic Stem Cells
Cell Proliferation
030304 developmental biology
Cell growth
lcsh:R
Cancer
medicine.disease
Embryonic stem cell
Cancer research
lcsh:Q
NODAL
Activin Receptors, Type I
Neoplasm Transplantation
Developmental Biology
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 7
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....939f4a34a0eb1ab098da805f97a0aaa1