|
|
The role of erbB-2 oncogene in the biology of cancer stem-like cells
Prokopová, Kateřina ; Neužil, Jiří (advisor) ; Anděra, Ladislav (referee)
Recent studies indicate the existence of a subpopulation of cells within tumours with stem cell-like characteristics. These "cancer stem-like cells" (CSCs) are relatively resistant to established therapies, usually targeting differentiated and fast proliferating cells. Therefore, CSCs may be a reason for the relapse of neoplastic diseases. CSCs can be characterised by a specific gene expression profile and deregulated signalling pathways. Of these, upregulation of the erbB-2 (HER2) receptor, a hallmark of ~25-30% breast cancer patients, is related to dismal prognosis, elevated proliferation potential and resistance to chemotherapy. Recent evidence has suggested that upregulation of erbB-2 leads to increase in the pool of CSCs. In our study we used mammospheres, cells grown in the absence of serum, an in vitro model of breast CSCs, which were prepared by "weaning" breast cancer MCF7 cells to a special medium. These cells were CD44high and showed increased expression of ABCG-2, Sox-2, Vimentin as well as high levels of erbB-2. Next, we prepared a stable line of MCF7 cells with low levels of erbB-2 by shRNA. ErbB-2low cells were characterised for expression of set of CSCs markers and tested for tumour forming efficacy in nude mice using ultrasound imaging. Keywords Cancer stem-like cells, erbB-2,...
|
|
|
The role of erbB-2 oncogene in the biology of cancer stem-like cells
Prokopová, Kateřina ; Neužil, Jiří (advisor) ; Anděra, Ladislav (referee)
Recent studies indicate the existence of a subpopulation of cells within tumours with stem cell-like characteristics. These "cancer stem-like cells" (CSCs) are relatively resistant to established therapies, usually targeting differentiated and fast proliferating cells. Therefore, CSCs may be a reason for the relapse of neoplastic diseases. CSCs can be characterised by a specific gene expression profile and deregulated signalling pathways. Of these, upregulation of the erbB-2 (HER2) receptor, a hallmark of ~25-30% breast cancer patients, is related to dismal prognosis, elevated proliferation potential and resistance to chemotherapy. Recent evidence has suggested that upregulation of erbB-2 leads to increase in the pool of CSCs. In our study we used mammospheres, cells grown in the absence of serum, an in vitro model of breast CSCs, which were prepared by "weaning" breast cancer MCF7 cells to a special medium. These cells were CD44high and showed increased expression of ABCG-2, Sox-2, Vimentin as well as high levels of erbB-2. Next, we prepared a stable line of MCF7 cells with low levels of erbB-2 by shRNA. ErbB-2low cells were characterised for expression of set of CSCs markers and tested for tumour forming efficacy in nude mice using ultrasound imaging. Keywords Cancer stem-like cells, erbB-2,...
|
guest ::
