title: Deciphering cancer complexities in genetically engineered mice.
abstract: 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.
authors.affiliation: University of North Carolina School of Medicine, Chapel Hill, 27599, USA.
authors.forename: K
authors.initials: K
authors.lastname: Simin
authors.forename: R
authors.initials: R
authors.lastname: Hill
authors.forename: Y
authors.initials: Y
authors.lastname: Song
authors.forename: Q
authors.initials: Q
authors.lastname: Zhang
authors.forename: R
authors.initials: R
authors.lastname: Bash
authors.forename: R D
authors.initials: RD
authors.lastname: Cardiff
authors.forename: C
authors.initials: C
authors.lastname: Yin
authors.forename: A
authors.initials: A
authors.lastname: Xiao
authors.forename: K
authors.initials: K
authors.lastname: McCarthy
authors.forename: T
authors.initials: T
authors.lastname: van Dyke
mesh_terms: D000818:Animals; D001254:Astrocytoma / Q000209:etiology / Q000235:genetics / Q000473:pathology; D005260:Female; D016161:Genes, Retinoblastoma; D011905:Genes, ras; D005818:Genetic Engineering; D005822:Genetic Vectors; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D051059:PTEN Phosphohydrolase / Q000037:antagonists & inhibitors / Q000235:genetics; D011471:Prostatic Neoplasms / Q000209:etiology / Q000235:genetics / Q000473:pathology; D016160:Retinoblastoma Protein / Q000037:antagonists & inhibitors
chemical_list: D016160:Retinoblastoma Protein; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse