TY - JOUR
T1 - Deciphering cancer complexities in genetically engineered mice
AU - Simin, K.
AU - Hill, R.
AU - Song, Y.
AU - Zhang, Q.
AU - Bash, R.
AU - Cardiff, Robert
AU - Yin, C.
AU - Xiao, A.
AU - McCarthy, K.
AU - Van Dyke, T.
PY - 2005/12/1
Y1 - 2005/12/1
N2 - Because the pRb pathway is disrupted in most solid human cancers, we have generated genetically engineered mouse cancer models by inactivating pRb function in several cell types, including astrocytes and mammary, prostate, ovarian, and brain choroid plexus epithelia. In every case, proliferation and apoptosis are acutely induced, predisposing to malignancy. Cell type dictates the pathways involved in tumor progression. In the astrocytoma model, we developed strategies to induce events in the adult brain, either throughout the tissue or focally. Both K-Ras activation and Pten inactivation play significant roles in progression. In the prostate model, adenocarcinoma progression depends on Pten inactivation. However, nonautonomous induction of p53 in the mesenchyme leads to evolution of both compartments, with p53 loss occurring in the mesenchyme. Thus, studies in these models continue to identify key tumorigenesis mechanisms. Furthermore, we are hopeful that the models will provide useful preclinical systems for diagnostic and therapeutic development.
AB - Because the pRb pathway is disrupted in most solid human cancers, we have generated genetically engineered mouse cancer models by inactivating pRb function in several cell types, including astrocytes and mammary, prostate, ovarian, and brain choroid plexus epithelia. In every case, proliferation and apoptosis are acutely induced, predisposing to malignancy. Cell type dictates the pathways involved in tumor progression. In the astrocytoma model, we developed strategies to induce events in the adult brain, either throughout the tissue or focally. Both K-Ras activation and Pten inactivation play significant roles in progression. In the prostate model, adenocarcinoma progression depends on Pten inactivation. However, nonautonomous induction of p53 in the mesenchyme leads to evolution of both compartments, with p53 loss occurring in the mesenchyme. Thus, studies in these models continue to identify key tumorigenesis mechanisms. Furthermore, we are hopeful that the models will provide useful preclinical systems for diagnostic and therapeutic development.
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U2 - 10.1101/sqb.2005.70.038
DO - 10.1101/sqb.2005.70.038
M3 - Article
C2 - 16869764
AN - SCOPUS:33746388298
VL - 70
SP - 283
EP - 290
JO - Cold Spring Harbor Symposia on Quantitative Biology
JF - Cold Spring Harbor Symposia on Quantitative Biology
SN - 0091-7451
ER -