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Ron receptor signaling augments mammary tumor formation and metastasis in a murine model of breast cancer.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Toney-Earley, Kenya Waltz, Susan E. |
| Copyright Year | 2005 |
| Abstract | The tyrosine kinase receptor Ron has been implicated in several types of cancer, including overexpression in human breast cancer. This is the first report describing the effect of Ron signaling on tumorigenesis and metastasis in a mouse model of breast cancer. Mice with a targeted deletion of the Ron tyrosine kinase signaling domain (TK-/-) were crossed to mice expressing the polyoma virus middle T antigen (pMT) under the control of the mouse mammary tumor virus promoter. Both pMT-expressing wild-type control (pMT+/- TK+/+) and pMT+/- TK-/- mice developed mammary tumors and lung metastases. However, a significant decrease in mammary tumor initiation and growth was found in the pMT+/- TK-/- mice compared with controls. An examination of mammary tumors showed that there was a significant decrease in microvessel density, significantly decreased cellular proliferation, and a significant increase in terminal deoxynucleotidyl transferase-mediated nick end labeling-positive staining in mammary tumor cells from the pMT+/- TK-/- mice compared with the pMT+/- TK+/+ mice. Biochemical analyses on mammary tumor lysates showed that whereas both the pMT-expressing TK+/+ and TK-/- tumors have increased Ron expression compared with normal mammary glands, the pMT-expressing TK-/- tumors have deficits in mitogen-activated protein kinase and AKT activation. These results indicate that Ron signaling synergizes with pMT signaling to induce mammary tumor formation, growth, and metastasis. This effect may be mediated in part through the regulation of angiogenesis and through proliferative and cell survival pathways regulated by mitogen-activated protein kinase and AKT. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://cancerres.aacrjournals.org/content/65/4/1285.full.pdf |
| Alternate Webpage(s) | http://cancerres.aacrjournals.org/content/canres/65/4/1285.full.pdf |
| PubMed reference number | 15735014v1 |
| Volume Number | 65 |
| Issue Number | 4 |
| Journal | Cancer research |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Animal Mammary Neoplasms Carcinogenesis Cell Proliferation Cell Survival DNA Nucleotidylexotransferase Deletion Mutation Hyperplasia Lung diseases Mammary gland Microvessels Mitogen-Activated Protein Kinases Mitogens Murine sarcoma viruses Neoplasm Metastasis Oncogenic Viruses Pituitary Neoplasms Polyomavirus Protein Tyrosine Kinase Proto-Oncogene Proteins c-akt Transferase Tumor Initiation |
| Content Type | Text |
| Resource Type | Article |
