Medical College of Wisconsin
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Decreased androgen-responsive growth of human prostate cancer is associated with increased genetic alterations. Clin Cancer Res 2001 Nov;7(11):3472-80

Date

11/14/2001

Pubmed ID

11705865

Scopus ID

2-s2.0-0035175919   32 Citations

Abstract

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.

Author List

Karan D, Schmied BM, Dave BJ, Wittel UA, Lin MF, Batra SK

Author

Dev Karan PhD Associate Professor in the Pathology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Androgens
Animals
Cell Division
DNA, Neoplasm
Female
Humans
Karyotyping
Loss of Heterozygosity
Male
Mice
Mice, Nude
Microsatellite Repeats
Neoplasm Transplantation
Prostatic Neoplasms
Time Factors
Transplantation, Heterologous
Tumor Cells, Cultured