Species- and cell type-specific requirements for cellular transformation.

By Annapoorni Rangarajan, Sue-Jean Hong, A. Gifford, R. Weinberg. Cancer Cell, 2004

602 citations recorded by the source corpus.

Recent evidence suggests that human cells require more genetic changes for neoplastic transformation than do their murine counterparts. However, a precise enumeration of these differences has never been undertaken. We have determined that perturbation of two signaling pathways-involving p53 and Raf-suffices for the tumorigenic conversion of normal murine fibroblasts, while perturbation of six pathways-involving p53, pRb, PP2A, telomerase, Raf, and Ral-GEFs-is needed for human fibroblasts. Cell type-specific differences also exist in the requirements for tumorigenic transformation: immortalized human fibroblasts require the activation of Raf and Ral-GEFs, human embryonic kidney cells require the activation of PI3K and Ral-GEFs, and human mammary epithelial cells require the activation of Raf, PI3K, and Ral-GEFs.

Subfields: Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/06ed0643de83eb4628b3d139a1554d4a79c5768e

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Citations in the corpus

CIP2A inhibits PP2A in human malignancies. (2007, positive): “Experimentally, it has been demonstrated that activation of Ras and telomerase, along with inactivation of the tumor suppressor proteins p53 and retinoblastoma protein (Rb) can immortalize a variety of human cell types, which can subsequently transform to a tumorigenic state only by inhibiting prote”
Modelling breast cancer: one size does not fit all (2007, background): “Furthermore, there is an ongoing debate as to whether the same genetic alterations transform both mouse and human epithelial cell”
Capturing complex 3D tissue physiology in vitro (2006, background): “Furthermore, fundamental differences in telomerase regulation between rodents and human”
Integrative genomic approaches identify IKBKE as a breast cancer oncogene. (2007, background): “quently observed in other malignancies such as melanoma, these observations are consistent with the view that particular combinations of Ras effector pathway mutations cooperate in specific cell types (Rangarajan et al., 2004).”
Phosphatase‐mediated crosstalk between MAPK signaling pathways in the regulation of cell survival (2008, background): “Moreover, in human fibroblasts and mammary epithelial cells, Ras-mediated activation of Raf was identified as one of the requirements for transformation (19).”
Regulation of the INK4b–ARF–INK4a tumour suppressor locus: all for one or one for all (2006, background): “As alluded to above, this has echoes in the more prominent role of Arf in mouse cell senescence and might reflect differences in the operation of the signalling pathways in the two specie”
Modeling tissue morphogenesis and cancer in 3D. (2007, positive): “Because rodents or other animals can metabolize and respond to drugs differently than humans (Rangarajan et al., 2004), using human 3D tissue surrogates for “in vivo-like” drug testing might help reduce the high failure rate in the development of new drugs.”
Role of chemokines in tumor growth. (2007, background): “Interestingly, the threshold number of mutations that are needed to transform normal human cells is greater than that required for murine cells [16].”