Under Pressure: Stromal Fibroblasts Change Their Ways

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Under Pressure: Stromal Fibroblasts Change Their Ways Brian Bierie, Harold L. Moses  Cell  Volume 123, Issue 6, Pages 985-987 (December 2005) DOI: 10.1016/j.cell.2005.11.029 Copyright © 2005 Elsevier Inc. Terms and Conditions

Figure 1 The Carcinoma Epithelium Selects for p53 Null Stromal Fibroblasts Expression of a fragment of the SV40 T antigen (TgAPT121) in the epithelium leads to suppression of retinoblastoma protein family members. Paracrine signaling by the epithelium then induces an upregulation in p53 expression in stromal fibroblasts, resulting in decreased fibroblast proliferation. Under this selective pressure, fibroblasts that have lost p53 are expanded. These carcinoma-associated fibroblasts contribute to tumor progression and the eventual loss of p53 in the epithelium. Multiple changes in stromal fibroblasts are known to contribute to tumor progression, including altered gene expression (for example, enhanced expression of SDF-1), loss of heterozygosity (for example, as frequently occur at 11q), and specific mutations (such as those that inactivate p53 or PTEN). Cell 2005 123, 985-987DOI: (10.1016/j.cell.2005.11.029) Copyright © 2005 Elsevier Inc. Terms and Conditions