Multipotent mammary cancer stem cells integrate stem cell and clonal expansion theories of tumor progression

ABSTRACT: The diversity of human breast cancer subtypes has led to the hypothesis that breast cancer is a number of different diseases arising from cells at various stages of differentiation. We have derived clonal multipotent metastatic mammary cancer stem cells from the polyomavirus middle T mouse model of breast cancer, that can differentiate into luminal, myoepithelial and alveolar cells. When injected orthotopically at low-density, the resulting tumors express estrogen and progesterone receptors. With continued passage in vivo, the tumor cells undergo additional epigenetic and/or genetic changes that result in upregulation of Her2 expression or clonal expansion of cells that give rise to basal-like or claudin-low tumors. As in human tumors, the more aggressive tumor subtypes express nuclear p53. The temporal sequence of events suggests that contrary to current dogma, multiple tumor subtypes can originate from a single multipotent cancer stem cell that undergoes evolution during tumor progression. Furthermore, these data raise the possibility that a human polyomavirus may be a causative agent in spontaneous forms of human breast cancer. Three spontaneous PyVmT tumors and forty cell line derived tumors were analyzed. To generate cell line derived tumors, 10^6 tumor cells were injected orthotopically into four abdominal mammary fat pads in syngeneic C57Bl/6 female mice. After 6-8 weeks the mice were euthanized and the tumors excised and frozen at -80°C. One tumor per mouse 8-10mm in diameter was used for array analysis. RNA was extracted using the RNeasy kit (Qiagen) with on column DNA removal.

ORGANISM(S): Mus musculus

SUBMITTER: Lesley Ellies 

PROVIDER: E-GEOD-61138 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress