Decreased androgen-responsive growth of human prostate cancer is associated with increased genetic alterations

D. Karan, B. M. Schmied, B. J. Dave, U. A. Wittel, M. F. Lin, S. K. Batra

Research output: Contribution to journalArticlepeer-review

34 Scopus citations


Genetic mechanisms involved in prostate tumor progression from the androgen-responsive to androgen-unresponsive stage are not well understood because of the tremendous heterogeneity in the tumor as well as the lack of suitable models. Using 165 repeat microsatellite DNA markers distributed equally over all of the chromosomes, we determined an association between genetic alterations and androgen-unresponsive growth in three stages of LNCaP cell model (C33: early, androgen-responsive; C51: mid, decreased androgen-responsive; and C81: late, androgen-unresponsive and increased tumorigenicity). Furthermore, the genetic alterations were confirmed in laser microdissected normal and cancerous tissues from 15 clinical samples of human prostatic adenocarcinomas using selected markers. A stem-line karyotype analysis exhibited an identical chromosomal pattern in both C33 and C81 stage cells except for the structural rearrangements of chromosome 3 and a gain of one copy of the Y chromosome in the androgen-unresponsive C81 stage cells. Nine microsatellite DNA markers on seven different chromosomes (1, 4, 5, 11, 17, 18, and 19) showed microsatellite instability (MSI) in both C51 and C81 stage cells. Additionally, 23 markers on 15 different chromosomes revealed MSI in C81 cells. Chromosomal regions demonstrating allelic loss (AL) include 1q, 3p, 5p, 8q, 9q, and 13q in C51 and C81 cells. In clinical human specimens, MSI was observed on chromosomes 1 (20%), 5 (23%), 17 (40%), and 19 (36%), whereas ALs were found 40% on chromosomal region 1q, 20% on 3p, 26% on 5p and 8q, and 33% on 13q. In conclusion, the LNCaP cell model showed the increasing number of genetic changes including MSI and AL. These increased genetic alterations may be associated with the development of the androgen-unresponsive phenotype.

Original languageEnglish (US)
Pages (from-to)3472-3480
Number of pages9
JournalClinical Cancer Research
Issue number11
StatePublished - 2001

ASJC Scopus subject areas

  • General Medicine


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