title: β1 integrin deletion enhances progression of prostate cancer in the TRAMP mouse model.
abstract: β1 integrin regulates the response of both normal and cancer cells to their local environment. Although mis-localised in prostate cancer, the role β1 integrin plays in prostate development and carcinogenesis remains unknown. To assess the role of β1 integrin in vivo, we conditionally deleted β1 integrin from prostate epithelium and subsequently crossed these mice to the TRAMP prostate carcinogenesis model. Deletion of β1 integrin following castration and subsequent androgen supplementation resulted in an expansion of the p63-positive basal cell population and decreased differentiation. Consistent with these findings, deletion of β1 integrin in TRAMP mice decreased animal survival, decreased retention of normal prostate morphology, increased the percentage of tissue with poorly differentiated carcinoma, and increased cell proliferation. This study demonstrates that β1 integrin regulates several aspects of normal prostate development and in contrast to its role in several other tissues, its loss is associated with increased rates of prostate tumour progression.
authors: Cancer Research Program, Garvan Institute of Medical Research, 384 Victoria St, Darlinghurst, NSW 2010, Australia
authors: Kim
authors: K
authors: Moran-Jones
authors: Anita
authors: A
authors: Ledger
authors: Matthew J
authors: MJ
authors: Naylor
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004195:Disease Models, Animal; D018450:Disease Progression; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D005260:Female; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009919:Orchiectomy; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D013739:Testosterone / Q000494:pharmacology
chemical_list: D019012:Integrin beta1; D013739:Testosterone