Unknown

Dataset Information

0

Dynamic and nuclear expression of PDGFR? and IGF-1R in alveolar Rhabdomyosarcoma.


ABSTRACT: Since the advent of tyrosine kinase inhibitors as targeted therapies in cancer, several receptor tyrosine kinases (RTK) have been identified as operationally important for disease progression. Rhabdomyosarcoma (RMS) is a malignancy in need of new treatment options; therefore, better understanding of the heterogeneity of RTKs would advance this goal. Here, alveolar RMS (aRMS) tumor cells derived from a transgenic mouse model expressing two such RTKs, platelet-derived growth factor (PDGFR)? and insulin-like growth factor (IGF)-1R, were investigated by fluorescence-activated cell sorting (FACS). Sorted subpopulations that were positive or negative for PDGFR? and IGF-1R dynamically altered their cell surface RTK expression profiles as early as the first cell division. Interestingly, a difference in total PDGFR? expression and nuclear IGF-1R expression was conserved in populations. Nuclear IGF-1R expression was greater than cytoplasmic IGF-1R in cells with initially high cell surface IGF-1R, and cells with high nuclear IGF-1R established tumors more efficiently in vivo. RNA interference-mediated silencing of IGF-1R in the subpopulation of cells initially harboring higher cell surface and total IGF-1R resulted in significantly reduced anchorage-independent colony formation as compared with cells with initially lower cell surface and total IGF-1R expression. Finally, in accordance with the findings observed in murine aRMS, human aRMS also had robust expression of nuclear IGF-1R.RTK expression status and subcellular localization dynamics are important considerations for personalized medicine.

SUBMITTER: Aslam MI 

PROVIDER: S-EPMC3834004 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

altmetric image

Publications


<h4>Unlabelled</h4>Since the advent of tyrosine kinase inhibitors as targeted therapies in cancer, several receptor tyrosine kinases (RTK) have been identified as operationally important for disease progression. Rhabdomyosarcoma (RMS) is a malignancy in need of new treatment options; therefore, better understanding of the heterogeneity of RTKs would advance this goal. Here, alveolar RMS (aRMS) tumor cells derived from a transgenic mouse model expressing two such RTKs, platelet-derived growth fac  ...[more]

Similar Datasets

| S-EPMC2813858 | biostudies-literature
2014-03-19 | E-GEOD-41675 | biostudies-arrayexpress
| S-EPMC4599293 | biostudies-literature
2014-03-19 | GSE41675 | GEO
| S-EPMC6162497 | biostudies-literature
| S-EPMC4007842 | biostudies-literature
| S-EPMC2752171 | biostudies-literature
| S-EPMC5729466 | biostudies-literature
| S-EPMC8906536 | biostudies-literature
| S-EPMC8084799 | biostudies-literature