Androgen-induced differentiation and tumorigenicity of human prostate epithelial cells.
Androgen ablation is the primary treatment modality for patients with metastatic prostate cancer; however, the role of androgen receptor signaling in prostate cancer development remains enigmatic. Using a series of genetically defined immortalized and tumorigenic human prostate epithelial cells, we found that introduction of the androgen receptor induced differentiation of transformed prostate epithelial cells to a luminal phenotype reminiscent of organ-confined prostate cancer when placed in the prostate microenvironment. Moreover, androgen receptor expression converted previously androgen-independent, tumorigenic prostate epithelial cells into cells dependent on testosterone for tumor formation. These observations indicate that androgen receptor expression is oncogenic and addictive for the human prostate epithelium.
Berger
Raanan
R
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Febbo
Phillip G
PG
Majumder
Pradip K
PK
Zhao
Jean J
JJ
Mukherjee
Shayan
S
Signoretti
Sabina
S
Campbell
K Thirza
KT
Sellers
William R
WR
Roberts
Thomas M
TM
Loda
Massimo
M
Golub
Todd R
TR
Hahn
William C
WC
D000728:Androgens / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004268:DNA-Binding Proteins; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D020869:Gene Expression Profiling; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D005810:Multigene Family; D011467:Prostate / Q000378:metabolism / Q000473:pathology* / Q000502:physiology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011944:Receptors, Androgen / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D019098:Telomerase / Q000235:genetics
D000728:Androgens; D004268:DNA-Binding Proteins; D011944:Receptors, Androgen; D019098:Telomerase