Selective evolution of stromal mesenchyme with p53 loss in response to epithelial tumorigenesis (Cell, 2005, 123:1001-1011)

報告日期: 2006/03/31
報告時間: 16:00/16:50
報告學生: 林佩儒
講評老師: 張敏政


Selective Evolution of Stromal Mesenchyme with p53 Loss in Response to Epithelial Tumorigenesis


Cell 123: 1001-1011, 2005.


Speaker: 林佩儒                           Time: March. 31, 2005, 16:00-16:50

Commentator: 張敏政 教授        Place: Room 602



        The concept of epithelial-mesenchymal interaction is concerned in embryonic development and tumorigenesis. Crosstalk between carcinoma epithelial cells and mesenchyme may build a selective stress of a tumor micoenvironment and promote the tumorigenic properties of the epithelial compartment. The p53 tumor-suppressor protein is frequently mutated in carcinoma cells. Previous studies showed that loss of p53 in fibroblasts induced tumor progression in adjacent epithelial cell populations. Spontaneous prostate cancer models (TgAPT121 mice) develop extensive murine prostatic intraepithelial neoplasia (mPIN) as a result of inactivating pRb in prostate epithelium by N-terminal fragment of SV40 large T antigen. In TgAPT121 mice with alterations in the p53 genotype, p53 deficiency accelerates the onset of mPIN and stromal tumor development. Paracrine signaling from epithelium induces an upregulation of p53 expression, causing suppressed fibroblast proliferation and the eventual loss of p53 in TgAPT121;p53+/+ and TgAPT121;p53+/- prostatic mesenchyme. The stromal fibroblasts show proliferative performance in a TgAPT121;p53-/- background. These processes create a selective pressure for carcinoma-associated fibroblasts to promote the expansion of a subpopulation of fibroblasts that lack p53, then contributing to tumor progression.



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