Expression profiles of androgen independent bone metastatic prostate cancer cells indicate up-regulation of the putative serine-threonine kinase GS3955.
OBJECTIVE
We established gene expression profiles by gene array analysis in the LNCaP model of human prostate cancer progression and evaluated genes differentially expressed in the androgen independent and bone metastatic C4-2 cell line compared to the androgen dependent and nonmetastatic parental LNCaP cell line.


METHODS
Gene expression profiles were generated using Atlas cDNA arrays (Clontech, Palo Alto, California), comprising 1,176 genes. Intrinsic expression of the novel serine/threonine kinase GS3955 in LNCaP, C4-2 and PC-3 prostate cancer cells, and expression when stimulated with growth factors, was monitored by real-time reverse transcriptase-polymerase chain reaction. Furthermore, expression in human tumor specimens was evaluated. Cellular localization of GS3955 protein was analyzed by expressing it as a fusion with green fluorescent protein.


RESULTS
Comparable numbers of genes were up-regulated and down-regulated in C4-2 compared to LNCaP. The novel serine/threonine kinase GS3955 was markedly up-regulated (greater than 40-fold) in C4-2, differentially regulated in LNCaP and C4-2 by insulin-like growth factor-1, and variably expressed in human prostate tumor specimens. Moreover, GS3955 was shown to localize in the cell cytoplasm and nucleus.


CONCLUSIONS
Differential expression and mitogenic regulation of the serine/threonine kinase GS3955 in LNCaP and C4-2 suggest its functional involvement in the development of androgen independence and/or metastatic potential. GS3955 is also expressed in human prostate cancer specimens and further analysis may provide insights into the biology of prostate cancer progression.
Bisoffi
Marco
M
Department of Biochemistry and Molecular Biology, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA.
Klima
Irena
I
Gresko
Ekaterina
E
Durfee
Paul N
PN
Hines
William C
WC
Griffith
Jeffrey K
JK
Studer
Urs E
UE
Thalmann
George N
GN
D000728:Androgens / Q000378:metabolism; D001859:Bone Neoplasms / Q000556:secondary*; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018450:Disease Progression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D000728:Androgens; D006133:Growth Substances; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C489044:TRIB2 protein, human