Identification of androgen-coregulated protein networks from the microsomes of human prostate cancer cells.
BACKGROUND
Androgens play a critical role in the development of prostate cancer-dysregulation of androgen-regulated growth pathways can led to hormone-refractory prostate cancer. A comprehensive understanding of androgen-regulated cellular processes has not been achieved to date. To this end, we have applied a large-scale proteomic approach to define cellular processes that are responsive to androgen treatment in LNCaP prostate cancer cells.


RESULTS
Using isotope-coded affinity tags and mass spectrometry we identified and quantified the relative abundance levels of 1,064 proteins and found that distinct cellular processes were coregulated by androgen while others were essentially unaffected. Subsequent pharmacological perturbation of the cellular process for energy generation confirmed that androgen starvation had a profound effect on this pathway.


CONCLUSIONS
Our results provide evidence for the role of androgenic hormones in coordinating the expression of critical components involved in distinct cellular processes and further establish a foundation for the comprehensive reconstruction of androgen-regulated protein networks and pathways in prostate cancer cells.
Wright
Michael E
ME
Institute for Systems Biology, Seattle, WA 98103, USA.
Eng
Jimmy
J
Sherman
James
J
Hockenbery
David M
DM
Nelson
Peter S
PS
Galitski
Timothy
T
Aebersold
Ruedi
R
D000595:Amino Acid Sequence / Q000235:genetics; D000728:Androgens / Q000502:physiology*; D045744:Cell Line, Tumor; D004734:Energy Metabolism / Q000235:genetics; D006801:Humans; D050356:Lipid Metabolism; D008297:Male; D008861:Microsomes / Q000737:chemistry* / Q000378:metabolism*; D008969:Molecular Sequence Data; D017430:Prostate-Specific Antigen / Q000737:chemistry / Q000235:genetics; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014176:Protein Biosynthesis; D011506:Proteins / Q000145:classification / Q000378:metabolism; D020543:Proteome / Q000096:biosynthesis / Q000145:classification / Q000378:metabolism; D040901:Proteomics / Q000379:methods
D000728:Androgens; D011506:Proteins; D020543:Proteome; D017430:Prostate-Specific Antigen