title: Molecular alterations in primary prostate cancer after androgen ablation therapy.
abstract: OBJECTIVE
  After an initial response to androgen ablation, most prostate tumors recur, ultimately progressing to highly aggressive androgen-independent cancer. The molecular mechanisms underlying progression are not well known in part due to the rarity of androgen-independent samples from primary and metastatic sites.
  
  
  METHODS
  We compared the gene expression profiles of 10 androgen-independent primary prostate tumor biopsies with 10 primary, untreated androgen-dependent tumors. Samples were laser capture microdissected, the RNA was amplified, and gene expression was assessed using Affymetrix Human Genome U133A GeneChip. Differential expression was examined with principal component analysis, hierarchical clustering, and Student's t testing. Analysis of gene ontology was done with Expression Analysis Systematic Explorer and gene expression data were integrated with genomic alterations with Differential Gene Locus Mapping.
  
  
  RESULTS
  Unsupervised principal component analysis showed that the androgen-dependent and androgen-independent tumors segregated from one another. After filtering the data, 239 differentially expressed genes were identified. Two main gene ontologies were found discordant between androgen-independent and androgen-dependent tumors: macromolecule biosynthesis was down-regulated and cell adhesion was up-regulated in androgen-independent tumors. Other differentially expressed genes were related to interleukin-6 signaling as well as angiogenesis, cell adhesion, apoptosis, oxidative stress, and hormone response. The Differential Gene Locus Mapping analysis identified nine regions of potential chromosomal deletion in the androgen-independent tumors, including 1p36, 3p21, 6p21, 8p21, 11p15, 11q12, 12q23, 16q12, and 16q21.
  
  
  CONCLUSIONS
  Taken together, these data identify several unique characteristics of androgen-independent prostate cancer that may hold potential for the development of targeted therapeutic intervention.
authors.affiliation: Pathogenetics Unit, Laboratory of Pathology, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA. bestcar@mail.nih.gov
authors.forename: Carolyn J M
authors.initials: CJ
authors.lastname: Best
authors.forename: John W
authors.initials: JW
authors.lastname: Gillespie
authors.forename: Yajun
authors.initials: Y
authors.lastname: Yi
authors.forename: Gadisetti V R
authors.initials: GV
authors.lastname: Chandramouli
authors.forename: Mark A
authors.initials: MA
authors.lastname: Perlmutter
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Gathright
authors.forename: Heidi S
authors.initials: HS
authors.lastname: Erickson
authors.forename: Lauren
authors.initials: L
authors.lastname: Georgevich
authors.forename: Michael A
authors.initials: MA
authors.lastname: Tangrea
authors.forename: Paul H
authors.initials: PH
authors.lastname: Duray
authors.forename: Sergio
authors.initials: S
authors.lastname: González
authors.forename: Alfredo
authors.initials: A
authors.lastname: Velasco
authors.forename: W Marston
authors.initials: WM
authors.lastname: Linehan
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Matusik
authors.forename: Douglas K
authors.initials: DK
authors.lastname: Price
authors.forename: William D
authors.initials: WD
authors.lastname: Figg
authors.forename: Michael R
authors.initials: MR
authors.lastname: Emmert-Buck
authors.forename: Rodrigo F
authors.initials: RF
authors.lastname: Chuaqui
mesh_terms: D000368:Aged; D000726:Androgen Antagonists / Q000378:metabolism; D000728:Androgens / Q000378:metabolism*; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D001706:Biopsy; D002448:Cell Adhesion; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002875:Chromosomes / Q000648:ultrastructure; D016000:Cluster Analysis; D018450:Disease Progression; D015536:Down-Regulation; D017353:Gene Deletion; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D016678:Genome; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D007834:Lasers; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D009362:Neoplasm Metastasis; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress; D025341:Principal Component Analysis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D012313:RNA / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D000726:Androgen Antagonists; D000728:Androgens; D018931:Antineoplastic Agents, Hormonal; D015850:Interleukin-6; D012313:RNA