Project description:We previously reported the isolation and in vitro propagation of highly tumorigenic mammospheres (MCFS) isolated from MCF7 breast cancer cell line. In this study we obtained gene expression profiles of MCFS and parental MCF7 cell lines using SOLiD RNA-sequencing after linear isothermal DNA amplification.
Project description:We have generated tumorigenic (S2N) and non-tumorigenic (S2), normal-like to basal-like breast cancer cell lines from primary tumors. At high in vivo inoculation cell numbers of 10^6 cells/mouse both S2N and S2 monolayer as well as sphere culture cells grew at similar rates. However, at low inoculation cell numbers down to 10^3 cells only S2N sphere cells generated xenograft tumors. mRNA profiling revealed a unique cluster pattern of the tumorigenic S2N sphere cells, but a detailed analysis of TIC relevant transcription factors like Oct3, Sox and Nanog family members, Myc, Slug or Twist1 revealed no consistently increased expression in the highly tumorigenic cell lines. Our data indicate that the intrinsic genetic and functional markers investigated are not solely indicative of the in vivo tumorigenicity of putative breast tumor-initiating cells. 4 samples with 3 replicates each
Project description:Bulk cancer cell populations are known to display distinct metabolic properties compared to their normal counterparts. However, relatively little is known about heterogeneity of metabolic properties within tumors. In this study we show that, analogous to some normal stem cells, breast tumor initiating cells (TICs, also called cancer stem cells) have distinct metabolic properties compared to non-tumorigenic cancer cells (NTCs). Transcriptome profiling using RNA-Seq revealed TICs under-express genes involved in mitochondrial oxidative phosphorylation and although TICs are relatively quiescent, they preferentially perform glycolysis over oxidative phosphorylation compared to NTCs. TICs contain fewer mitochondria and display lower expression and activity of pyruvate dehydrogenase (Pdh), a key regulator of oxidative phosphorylation. Metabolic reprogramming of TICs by pharmacologic activation of Pdh preferentially eliminates TICs in vitro and in vivo. Our findings reveal unique metabolic properties of TICs and indicate that metabolic reprogramming represents a promising strategy for targeting these cells. Examination transcriptome profiles for breast tumor initiating cells (TICs) and non-tumorigenic cells (NTCs)
Project description:We have generated tumorigenic (S2N) and non-tumorigenic (S2), normal-like to basal-like breast cancer cell lines from primary tumors. At high in vivo inoculation cell numbers of 10^6 cells/mouse both S2N and S2 monolayer as well as sphere culture cells grew at similar rates. However, at low inoculation cell numbers down to 10^3 cells only S2N sphere cells generated xenograft tumors. mRNA profiling revealed a unique cluster pattern of the tumorigenic S2N sphere cells, but a detailed analysis of TIC relevant transcription factors like Oct3, Sox and Nanog family members, Myc, Slug or Twist1 revealed no consistently increased expression in the highly tumorigenic cell lines. Our data indicate that the intrinsic genetic and functional markers investigated are not solely indicative of the in vivo tumorigenicity of putative breast tumor-initiating cells.
