title: Lineage analysis of basal epithelial cells reveals their unexpected plasticity and supports a cell-of-origin model for prostate cancer heterogeneity.
abstract: A key issue in cancer biology is whether oncogenic transformation of different cell types of origin within an adult tissue gives rise to distinct tumour subtypes that differ in their prognosis and/or treatment response. We now show that initiation of prostate tumours in basal or luminal epithelial cells in mouse models results in tumours with distinct molecular signatures that are predictive of human patient outcomes. Furthermore, our analysis of untransformed basal cells reveals an unexpected assay dependence of their stem cell properties in sphere formation and transplantation assays versus genetic lineage tracing during prostate regeneration and adult tissue homeostasis. Although oncogenic transformation of basal cells gives rise to tumours with luminal phenotypes, cross-species bioinformatic analyses indicate that tumours of luminal origin are more aggressive than tumours of basal origin, and identify a molecular signature associated with patient outcome. Our results reveal the inherent plasticity of basal cells, and support a model in which different cells of origin generate distinct molecular subtypes of prostate cancer.
authors: Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
authors: Zhu A
authors: ZA
authors: Wang
authors: Antonina
authors: A
authors: Mitrofanova
authors: Sarah K
authors: SK
authors: Bergren
authors: Cory
authors: C
authors: Abate-Shen
authors: Robert D
authors: RD
authors: Cardiff
authors: Andrea
authors: A
authors: Califano
authors: Michael M
authors: MM
authors: Shen
mesh_terms: D000328:Adult; D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D002280:Basal Cell Carcinoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D017930:Genes, Reporter; D006801:Humans; D007124:Immunoenzyme Techniques; D053555:Keratin-5 / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D051059:PTEN Phosphohydrolase / Q000502:physiology; D010766:Phosphorylation; D011467:Prostate / Q000166:cytology* / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D053555:Keratin-5; D012333:RNA, Messenger; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse