title: Identification of genes potentially involved in the acquisition of androgen-independent and metastatic tumor growth in an autochthonous genetically engineered mouse prostate cancer model.
abstract: BACKGROUND
  A major focus of prostate cancer research has been to identify genes that are deregulated during tumor progression, potentially providing diagnostic markers and therapeutic targets.
  
  
  METHODS
  We have employed serial analysis of gene expression (SAGE) and microarray hybridization to identify alterations that occur during malignant transformation in the Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model. Many of these alterations were validated by real-time PCR (rtPCR).
  
  
  RESULTS
  We identified several hundred mRNAs that were deregulated. Cluster analysis of microarray profiles with samples from various stages of the disease demonstrated that androgen-independent (AI) primary tumors are similar to metastases; 180 transcripts have expression patterns suggesting an involvement in the genesis of late-stage tumors, and our data support a role for phospholipase A2 group IIA in the acquisition of their highly aggressive characteristics.
  
  
  CONCLUSIONS
  Our analyses identified well-characterized genes that were previously known to be involved in prostate cancer, validating our study, and also uncovered transcripts that had not previously been implicated in prostate cancer progression.
authors.affiliation: Department of Oncology Research, Genzyme Corporation, Framingham, MA 01701-9322, USA. sharon.morgenbesser@genzyme.com
authors.forename: Sharon D
authors.initials: SD
authors.lastname: Morgenbesser
authors.forename: Rajashree P
authors.initials: RP
authors.lastname: McLaren
authors.forename: Brenda
authors.initials: B
authors.lastname: Richards
authors.forename: Mindy
authors.initials: M
authors.lastname: Zhang
authors.forename: Viatcheslav R
authors.initials: VR
authors.lastname: Akmaev
authors.forename: Scott F
authors.initials: SF
authors.lastname: Winter
authors.forename: Nora D
authors.initials: ND
authors.lastname: Mineva
authors.forename: Paula J
authors.initials: PJ
authors.lastname: Kaplan-Lefko
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Foster
authors.forename: Brian P
authors.initials: BP
authors.lastname: Cook
authors.forename: Michael R
authors.initials: MR
authors.lastname: Dufault
authors.forename: Xiahong
authors.initials: X
authors.lastname: Cao
authors.forename: Clarence J
authors.initials: CJ
authors.lastname: Wang
authors.forename: Beverly A
authors.initials: BA
authors.lastname: Teicher
authors.forename: Katherine W
authors.initials: KW
authors.lastname: Klinger
authors.forename: Norman M
authors.initials: NM
authors.lastname: Greenberg
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Madden
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism; D000728:Androgens / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D052138:Genes, Neoplasm / Q000502:physiology*; D005818:Genetic Engineering / Q000379:methods*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D013045:Species Specificity
chemical_list: D000728:Androgens