Stem Cell and Neurogenic Gene-expression Profiles Link Prostate Basal Cells to Aggressive Prostate Cancer

Overview

Journal Nat Commun

Specialty Biology

Date 2016 Mar 1

PMID 26924072

Citations 131

Authors

Dingxiao Zhang

Daechan Park

Yi Zhong

Yue Lu

Kiera Rycaj

Shuai Gong

Xin Chen

Xin Liu

Hsueh-Ping Chao

Pamela Whitney

Tammy Calhoun-Davis

Yoko Takata

Jianjun Shen

Vishwanath R Iyer

Dean G Tang

Affiliations

Soon will be listed here.

Abstract

The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. Here we describe a genome-wide transcriptome analysis of human benign prostatic basal and luminal epithelial populations using deep RNA sequencing. Through molecular and biological characterizations, we show that the differential gene-expression profiles account for their distinct functional properties. Strikingly, basal cells preferentially express gene categories associated with stem cells, neurogenesis and ribosomal RNA (rRNA) biogenesis. Consistent with this profile, basal cells functionally exhibit intrinsic stem-like and neurogenic properties with enhanced rRNA transcription activity. Of clinical relevance, the basal cell gene-expression profile is enriched in advanced, anaplastic, castration-resistant and metastatic prostate cancers. Therefore, we link the cell-type-specific gene signatures to aggressive subtypes of prostate cancer and identify gene signatures associated with adverse clinical features.

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References

Subramanian A, Tamayo P, Mootha V, Mukherjee S, Ebert B, Gillette M . Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005; 102(43):15545-50. PMC: 1239896. DOI: 10.1073/pnas.0506580102. View

Collins A, Habib F, Maitland N, Neal D . Identification and isolation of human prostate epithelial stem cells based on alpha(2)beta(1)-integrin expression. J Cell Sci. 2001; 114(Pt 21):3865-72. DOI: 10.1242/jcs.114.21.3865. View

Asangani I, Dommeti V, Wang X, Malik R, Cieslik M, Yang R . Therapeutic targeting of BET bromodomain proteins in castration-resistant prostate cancer. Nature. 2014; 510(7504):278-82. PMC: 4075966. DOI: 10.1038/nature13229. View

Ngan S, Stronach E, Photiou A, Waxman J, Ali S, Buluwela L . Microarray coupled to quantitative RT-PCR analysis of androgen-regulated genes in human LNCaP prostate cancer cells. Oncogene. 2009; 28(19):2051-63. DOI: 10.1038/onc.2009.68. View

Shen M, Abate-Shen C . Molecular genetics of prostate cancer: new prospects for old challenges. Genes Dev. 2010; 24(18):1967-2000. PMC: 2939361. DOI: 10.1101/gad.1965810. View

Valdez J, Zhang L, Su Q, Dakhova O, Zhang Y, Shahi P . Notch and TGFβ form a reciprocal positive regulatory loop that suppresses murine prostate basal stem/progenitor cell activity. Cell Stem Cell. 2012; 11(5):676-88. PMC: 3490134. DOI: 10.1016/j.stem.2012.07.003. View

Wang Z, Toivanen R, Bergren S, Chambon P, Shen M . Luminal cells are favored as the cell of origin for prostate cancer. Cell Rep. 2014; 8(5):1339-46. PMC: 4163115. DOI: 10.1016/j.celrep.2014.08.002. View

Nishino J, Kim I, Chada K, Morrison S . Hmga2 promotes neural stem cell self-renewal in young but not old mice by reducing p16Ink4a and p19Arf Expression. Cell. 2008; 135(2):227-39. PMC: 2582221. DOI: 10.1016/j.cell.2008.09.017. View

Ince T, Richardson A, Bell G, Saitoh M, Godar S, Karnoub A . Transformation of different human breast epithelial cell types leads to distinct tumor phenotypes. Cancer Cell. 2007; 12(2):160-70. DOI: 10.1016/j.ccr.2007.06.013. View

10.

Anders S, Huber W . Differential expression analysis for sequence count data. Genome Biol. 2010; 11(10):R106. PMC: 3218662. DOI: 10.1186/gb-2010-11-10-r106. View

11.

Trapnell C, Pachter L, Salzberg S . TopHat: discovering splice junctions with RNA-Seq. Bioinformatics. 2009; 25(9):1105-11. PMC: 2672628. DOI: 10.1093/bioinformatics/btp120. View

12.

Zhang D, Jiang P, Xu Q, Zhang X . Arginine and glutamate-rich 1 (ARGLU1) interacts with mediator subunit 1 (MED1) and is required for estrogen receptor-mediated gene transcription and breast cancer cell growth. J Biol Chem. 2011; 286(20):17746-54. PMC: 3093850. DOI: 10.1074/jbc.M110.206029. View

13.

Liu X, Chen X, Rycaj K, Chao H, Deng Q, Jeter C . Systematic dissection of phenotypic, functional, and tumorigenic heterogeneity of human prostate cancer cells. Oncotarget. 2015; 6(27):23959-86. PMC: 4695164. DOI: 10.18632/oncotarget.4260. View

14.

Tibshirani R, Hastie T, Narasimhan B, Chu G . Diagnosis of multiple cancer types by shrunken centroids of gene expression. Proc Natl Acad Sci U S A. 2002; 99(10):6567-72. PMC: 124443. DOI: 10.1073/pnas.082099299. View

15.

Trapnell C, Williams B, Pertea G, Mortazavi A, Kwan G, van Baren M . Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nat Biotechnol. 2010; 28(5):511-5. PMC: 3146043. DOI: 10.1038/nbt.1621. View

16.

Magnon C, Hall S, Lin J, Xue X, Gerber L, Freedland S . Autonomic nerve development contributes to prostate cancer progression. Science. 2013; 341(6142):1236361. DOI: 10.1126/science.1236361. View

17.

Wang Y, Wang Y, Liu Q, Xu G, Mao F, Qin T . Comparative RNA-seq analysis reveals potential mechanisms mediating the conversion to androgen independence in an LNCaP progression cell model. Cancer Lett. 2013; 342(1):130-8. DOI: 10.1016/j.canlet.2013.08.044. View

18.

Lawson D, Xin L, Lukacs R, Cheng D, Witte O . Isolation and functional characterization of murine prostate stem cells. Proc Natl Acad Sci U S A. 2006; 104(1):181-6. PMC: 1716155. DOI: 10.1073/pnas.0609684104. View

19.

Choi N, Zhang B, Zhang L, Ittmann M, Xin L . Adult murine prostate basal and luminal cells are self-sustained lineages that can both serve as targets for prostate cancer initiation. Cancer Cell. 2012; 21(2):253-65. PMC: 3285423. DOI: 10.1016/j.ccr.2012.01.005. View

20.

Delmore J, Issa G, Lemieux M, Rahl P, Shi J, Jacobs H . BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell. 2011; 146(6):904-17. PMC: 3187920. DOI: 10.1016/j.cell.2011.08.017. View