hTERT-immortalized prostate epithelial and stromal-derived cells: an authentic in vitro model for differentiation and carcinogenesis.
Prostate cancer is the most commonly diagnosed type of cancer in men, and there is no available cure for patients with advanced disease. In vitro model systems are urgently required to permit the study of human prostate cell differentiation and malignant transformation. Unfortunately, human prostate cells are particularly difficult to convert into continuously growing cultures. We report here the successful immortalization without viral oncogenes of prostate epithelial cells and, for the first time, prostate stromal cells. These cells exhibit a significant pattern of authentic prostate-specific features. In particular, the epithelial cell culture is able to differentiate into glandular buds that closely resemble the structures formed by primary prostate epithelial cells. The stromal cells have typical characteristics of prostate smooth muscle cells. These immortalized cultures may serve as a unique experimental platform to permit several research directions, including the study of cell-cell interactions in an authentic prostate microenvironment, prostate cell differentiation, and most significantly, the complex multistep process leading to prostate cell transformation.
Kogan
Ira
I
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
Goldfinger
Naomi
N
Milyavsky
Michael
M
Cohen
Merav
M
Shats
Igor
I
Dobler
Gabriele
G
Klocker
Helmut
H
Wasylyk
Bohdan
B
Voller
Maureen
M
Aalders
Tilly
T
Schalken
Jack A
JA
Oren
Moshe
M
Rotter
Varda
V
D000368:Aged; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002478:Cells, Cultured; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D006801:Humans; D008297:Male; D011467:Prostate / Q000166:cytology* / Q000378:metabolism* / Q000502:physiology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D019098:Telomerase / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics
D019941:Cyclin-Dependent Kinase Inhibitor p16; D004268:DNA-Binding Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D019098:Telomerase