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Structural alterations of chromosome 5 in twelve human prostate cancer cell lines
M Ozen1, N M Navone, A S Multani
1Department of Cell Biology, University of Texas M. D. Anderson Cancer Center 77030, USA.
Abstract:
Neoplastic transformation, cancer progression, and metastasis are determined by a series of well-defined changes that take place in target tissue cells. Genetic alterations associated with human prostate carcinogenesis are not well defined. Some chromosomal changes, including gain of chromosomes 7, 12, 17, and X and loss of heterozygosity in chromosomes 8p, 10q, 16q, 17p, and 18q, have been reported. We examined five newly established and eight previously established prostate cancer cell lines before and after subcutis and orthotopic injection into nude mice and observed that structural alterations of chromosome 5 were present in all of the cell lines except the parental LNCaP. The fluorescence in situ hybridization preparations with the use of whole chromosome 5 DNA painting probe confirmed our Giemsa-banding data. Alterations of chromosome 5 consisted of t(1;5)(p36;q15), t(5;?)(p11;?), del(5)(q23q35) in the SP2964(= ARCaP) cell line; t(5;8)(p15;q12), i(5)(p10), t(5;15)(q11;p11) in the SP3031 cell line; t(5;?;15) (q15;?;p11), t(5;7;14)(q31;p11-q32;q11), in the SP3173 and SP3241 cell lines (derived from the same patient); del(5)(q23-33) and t(5;7;14)(q31;p11-q32;q11) in the SP3316 cell line; t(3;5)(q21;q35) in the SP2884 cell line; t(5;5)(p15;q11) in the SP2356 cell line; i(5)(p10),t(5;?)(q23;?) in the DU-145 cell line; and i(5)(p10), t(5;?)(q11;?) and t(2;5)(q15;q15) in the PC-3 cell line. Because, in most cases, alteration of chromosome 5 resulted in the partial or complete loss of 5q, we conjectured that 5q might contain one or more tumor-suppressor genes for human prostate cancer development.
Insights
Structural alterations of chromosome 5 were found in most prostate cancer cell lines studied. These changes, particularly on the 5q arm, suggest the presence of tumor suppressor genes critical for prostate cancer development.
Area of Science:
- Oncology
- Human Genetics
- Cancer Biology
Background:
- Prostate cancer development involves genetic alterations, but specific chromosomal changes are not fully defined.
- Previous studies reported gains and losses in various chromosomes during prostate carcinogenesis.
- Understanding these genetic changes is crucial for identifying potential therapeutic targets.
Purpose of the Study:
- To investigate structural alterations of chromosome 5 in human prostate cancer cell lines.
- To determine if specific chromosomal changes in prostate cancer cell lines correlate with cancer progression.
- To identify potential tumor suppressor genes on chromosome 5 involved in prostate cancer.
Main Methods:
- Analysis of five newly established and eight previously established human prostate cancer cell lines.
- Examination of cell lines before and after in vivo implantation (subcutis and orthotopic) into nude mice.
- Giemsa-banding and fluorescence in situ hybridization (FISH) using whole chromosome 5 DNA painting probes to identify structural alterations.
Main Results:
- Structural alterations of chromosome 5 were detected in all tested prostate cancer cell lines, except for the parental LNCaP cell line.
- Specific alterations included translocations (t), isochromosomes (i), and deletions (del) involving chromosome 5.
- The majority of alterations resulted in partial or complete loss of the 5q arm.
Conclusions:
- Chromosome 5 structural alterations are common in human prostate cancer cell lines.
- The frequent loss of the 5q arm suggests it harbors tumor suppressor genes crucial for prostate cancer development.
- Further research is warranted to pinpoint specific genes on 5q involved in prostate carcinogenesis.