Establishment and characterization of androgen-independent human prostate cancer LNCaP cell model. Prostate 2002 Mar 01;50(4):222-35
Date
03/01/2002Pubmed ID
11870800DOI
10.1002/pros.10054Scopus ID
2-s2.0-0036187849 (requires institutional sign-in at Scopus site) 165 CitationsAbstract
BACKGROUND: The acquisition of an androgen-independent phenotype is the most serious issue of prostate cancer treatment. Although several experimental cell models have been reported for studying androgen independence, they have limited applications related to hormone-refractory prostate cancer. To investigate the molecular mechanism of androgen-independent growth of prostate cancer, we established a useful LNCaP cell model that resembles the clinical scenario of hormone-refractory prostate cancer.
METHODS: Androgen-sensitive LNCaP parental cells were continuously maintained in a regular cell-culture medium, that is, phenol red-positive RPMI 1640 medium supplemented with 5% fetal bovine serum and 1% glutamine. Upon passage, the androgen responsiveness of those cells decreased, to a level lower than that of parental cells. We examined the growth properties and androgen responsiveness of these different LNCaP cells in vitro and in vivo. Cytogenetic characteristics and expression of androgen receptors (ARs) and prostate-specific antigen (PSA) were determined.
RESULTS: Upon continuous passage, the biological behavior of parental C-33 cells (passage number less than 33) was altered. C-81 cells (passage number higher than 81) clearly exhibited more aggressive growth and lower androgen responsiveness than C-33 and C-51 cells (passage number between 35 and 80) in vitro and in vivo. Nevertheless, all these cells expressed a similar level of functional AR protein as well as a similar genetic profile. Moreover, in a steroid-reduced culture condition, C-81 cells secreted a higher level of PSA than C-33 cells.
CONCLUSIONS: Our LNCaP cell model closely recapitulates the progression of human prostate cancer from the androgen-responsive to the hormone-refractory state under the androgen nondeprived condition. This cell model may provide the opportunity to understand the molecular mechanisms associated with the acquisition of androgen independence during human prostate cancer progression.
Author List
Igawa T, Lin FF, Lee MS, Karan D, Batra SK, Lin MFAuthor
Dev Karan PhD Associate Professor in the Pathology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AndrogensAnimals
Blotting, Northern
Blotting, Western
Cytogenetic Analysis
DNA, Neoplasm
Female
Gene Expression Regulation, Neoplastic
Humans
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Neoplasms, Hormone-Dependent
Polymerase Chain Reaction
Prostate-Specific Antigen
Prostatic Neoplasms
Receptors, Androgen
Tumor Cells, Cultured
