Protein tyrosine kinase 6 regulates mammary gland tumorigenesis in mouse models
| Autor: | R R Franks, S M Ball-Kell, Maoyu Peng, A L Tyner, Hui Xie |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Genetically modified mouse
Cancer Research Transgene Mammary gland Biology medicine.disease_cause STAT3 03 medical and health sciences 0302 clinical medicine medicine ERBB2 Molecular Biology 030304 developmental biology 0303 health sciences Mouse mammary tumor virus Sik biology.organism_classification PTK6 3. Good health medicine.anatomical_structure 030220 oncology & carcinogenesis BRK STAT protein Cancer research Original Article Carcinogenesis Tyrosine kinase |
| Zdroj: | Oncogenesis |
| ISSN: | 2157-9024 |
| DOI: | 10.1038/oncsis.2013.43 |
| Popis: | Protein tyrosine kinase 6 (PTK6, also called BRK) is an intracellular tyrosine kinase expressed in the majority of human breast tumors and breast cancer cell lines, but its expression has not been reported in normal mammary gland. To study functions of PTK6 in vivo, we generated and characterized several transgenic mouse lines with expression of human PTK6 under control of the mouse mammary tumor virus (MMTV) long terminal repeat. Ectopic active PTK6 was detected in luminal epithelial cells of mature transgenic mammary glands. Lines expressing the MMTV-PTK6 transgene exhibited more than a two-fold increase in mammary gland tumor formation compared with nontransgenic control animals. PTK6 activates signal transducer and activator of transcription 3 (STAT3), and active STAT3 was detected in PTK6-positive mammary gland epithelial cells. Endogenous mouse PTK6 was not detected in the normal mouse mammary gland, but it was induced in mouse mammary gland tumors of different origin, including spontaneous tumors that developed in control mice, and tumors that formed in PTK6, H-Ras, ERBB2 and PyMT transgenic models. MMTV-PTK6 and MMTV-ERBB2 transgenic mice were crossed to explore crosstalk between PTK6 and ERBB2 signaling in vivo. We found no significant increase in tumor incidence, size or metastasis in ERBB2/PTK6 double transgenic mice. Although we detected increased proliferation in ERBB2/PTK6 double transgenic tumors, an increase in apoptosis was also observed. MMTV-PTK6 clearly promotes mammary gland tumorigenesis in vivo, but its impact may be underrepresented in our transgenic models because of induction of endogenous PTK6 expression. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|