Identification of genes potentially involved in the acquisition of androgen-independent and metastatic tumor growth in an autochthonous genetically engineered mouse prostate cancer model.
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.
Morgenbesser
Sharon D
SD
Department of Oncology Research, Genzyme Corporation, Framingham, MA 01701-9322, USA. sharon.morgenbesser@genzyme.com
McLaren
Rajashree P
RP
Richards
Brenda
B
Zhang
Mindy
M
Akmaev
Viatcheslav R
VR
Winter
Scott F
SF
Mineva
Nora D
ND
Kaplan-Lefko
Paula J
PJ
Foster
Barbara A
BA
Cook
Brian P
BP
Dufault
Michael R
MR
Cao
Xiahong
X
Wang
Clarence J
CJ
Teicher
Beverly A
BA
Klinger
Katherine W
KW
Greenberg
Norman M
NM
Madden
Stephen L
SL
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
D000728:Androgens