title: Conditionally ablated Pten in prostate basal cells promotes basal-to-luminal differentiation and causes invasive prostate cancer in mice.
abstract: Prostate glands comprise two major epithelial cell types: luminal and basal. Luminal cells have long been considered the cellular origin of prostate cancer (CaP). However, recent evidence from a prostate regeneration assay suggests that prostate basal cells can also give rise to CaP. Here, we characterize Pten-deficient prostate lesions arising from keratin 5-expressing basal cells in a temporally controlled system in mice. Pten-deficient prostate lesions arising from basal cells exhibited luminal phenotypes with higher invasiveness, and the cell fate of Pten-deficient basal cells was traced to neoplastic luminal cells. After temporally ablating Pten in keratin 8-expressing luminal cells, luminal-derived Pten-deficient prostate tumors exhibited slower disease progression, compared with basal-derived tumors, within 13 weeks after Pten ablation. Cellular proliferation was significantly increased in basal-derived versus luminal-derived Pten-deficient prostate lesions. Increased tumor invasion into the smooth muscle layer and aberrantly regulated aggressive signatures (Smad4 and Spp1) were identified exclusively in basal-derived Pten-deficient lesions. Interestingly, p63-expressing cells, which represent basal stem and progenitor cells of basal-derived Pten-deficient prostate lesions, were significantly increased, relative to cells of the luminal-derived prostate lesion. Furthermore, castration did not suppress cellular proliferation of either basal-derived or luminal-derived Pten-deficient prostate tumors. Taken together, our data suggest that, although prostate malignancy can originate from both basal and luminal populations, these two populations differ in aggressive potential.
authors: Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei, Taiwan.
authors: Tsai-Ling
authors: TL
authors: Lu
authors: Yi-Fen
authors: YF
authors: Huang
authors: Li-Ru
authors: LR
authors: You
authors: Nai-Chen
authors: NC
authors: Chao
authors: Fang-Yi
authors: FY
authors: Su
authors: Junn-Liang
authors: JL
authors: Chang
authors: Chun-Ming
authors: CM
authors: Chen
mesh_terms: D000728:Androgens / Q000172:deficiency; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D002369:Castration; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage; D049109:Cell Proliferation; D018450:Disease Progression; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm; D006801:Humans; D053555:Keratin-5; D053533:Keratin-8 / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009130:Muscle, Smooth / Q000473:pathology; D009361:Neoplasm Invasiveness; D051059:PTEN Phosphohydrolase / Q000172:deficiency / Q000378:metabolism*; D011467:Prostate / Q000378:metabolism / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D012038:Regeneration; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D000728:Androgens; D014408:Biomarkers, Tumor; D053555:Keratin-5; D053533:Keratin-8; D025521:Tumor Suppressor Proteins; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse