title: Conversion of Prostate Adenocarcinoma to Small Cell Carcinoma-Like by Reprogramming.
abstract: The lineage relationship between prostate adenocarcinoma and small cell carcinoma was studied by using the LuCaP family of xenografts established from primary neoplasm to metastasis. Expression of four stem cell transcription factor (TF) genes, LIN28A, NANOG, POU5F1, SOX2, were analyzed in the LuCaP lines. These genes, when force expressed in differentiated cells, can reprogram the recipients into stem-like induced pluripotent stem (iPS) cells. Most LuCaP lines expressed POU5F1, while LuCaP 145.1, representative of small cell carcinoma, expressed all four. Through transcriptome database query, many small cell carcinoma genes were also found in stem cells. To test the hypothesis that prostate cancer progression from "differentiated" adenocarcinoma to "undifferentiated" small cell carcinoma could involve re-expression of stem cell genes, the four TF genes were transduced via lentiviral vectors into five adenocarcinoma LuCaP lines-70CR, 73CR, 86.2, 92, 105CR-as done in iPS cell reprogramming. The resultant cells from these five transductions displayed a morphology of small size and dark appearing unlike the parentals. Transcriptome analysis of LuCaP 70CR* ("*" to denote transfected progeny) revealed a unique gene expression close to that of LuCaP 145.1. In a prostate principal components analysis space based on cell-type transcriptomes, the different LuCaP transcriptome datapoints were aligned to suggest a possible ordered sequence of expression changes from the differentiated luminal-like adenocarcinoma cell types to the less differentiated, more stem-like small cell carcinoma types, and LuCaP 70CR*. Prostate cancer progression can thus be molecularly characterized by loss of differentiation with re-expression of stem cell genes. J. Cell. Physiol. 231: 2040-2047, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Urology, University of Washington, Seattle, Washington.|Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington.|Pharmacy School, Federal University of Goiás, Goiânia, Brazil.
authors.forename: Gisely T
authors.initials: GT
authors.lastname: Borges
authors.affiliation: Department of Urology, University of Washington, Seattle, Washington.|Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington.|Department of Oral Pathology, Dental School, Federal University of Goiás, Goiânia, Brazil.
authors.forename: Eneida F
authors.initials: EF
authors.lastname: Vêncio
authors.affiliation: Department of Urology, University of Washington, Seattle, Washington.|Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington.
authors.forename: Sue-Ing
authors.initials: SI
authors.lastname: Quek
authors.affiliation: Department of Urology, University of Washington, Seattle, Washington.|Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington.
authors.forename: Adeline
authors.initials: A
authors.lastname: Chen
authors.affiliation: Department of Computing and Mathematics, FFCLRP, University of São Paulo, São Paulo, Brazil.
authors.forename: Diego M
authors.initials: DM
authors.lastname: Salvanha
authors.affiliation: Department of Computing and Mathematics, FFCLRP, University of São Paulo, São Paulo, Brazil.
authors.forename: Ricardo Z N
authors.initials: RZ
authors.lastname: Vêncio
authors.affiliation: Department of Urology, University of Washington, Seattle, Washington.
authors.forename: Holly M
authors.initials: HM
authors.lastname: Nguyen
authors.affiliation: Department of Urology, University of Washington, Seattle, Washington.|Puget Sound VA Medical Center, Seattle, Washington.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Vessella
authors.affiliation: Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington.|Department of Comparative Medicine, University of Washington, Seattle, Washington.
authors.forename: Christopher
authors.initials: C
authors.lastname: Cavanaugh
authors.affiliation: Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington.|Department of Comparative Medicine, University of Washington, Seattle, Washington.
authors.forename: Carol B
authors.initials: CB
authors.lastname: Ware
authors.affiliation: Institute for Systems Biology, Seattle, Washington.
authors.forename: Pamela
authors.initials: P
authors.lastname: Troisch
authors.affiliation: Department of Urology, University of Washington, Seattle, Washington.|Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington.
authors.forename: Alvin Y
authors.initials: AY
authors.lastname: Liu
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism*; D018288:Carcinoma, Small Cell / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics* / Q000502:physiology; D045744:Cell Line, Tumor; D065150:Cellular Reprogramming; D020869:Gene Expression Profiling / Q000379:methods; D005801:Genes, Homeobox / Q000235:genetics; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D008297:Male; D011467:Prostate / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays / Q000379:methods