Skip to main content

Advertisement

SpringerLink
Log in

Identification of a High Frequency of Chromosomal Rearrangements in the Centromeric Regions of Prostate Cancer Cell Lines by Sequential Giemsa Banding and Spectral Karyotyping

  • Original Research
  • Published:
Molecular Diagnosis Aims and scope Submit manuscript

Abstract

Background: Currently, prostate cancer (CaP) cytogenetics is not well defined, largely because of technical difficulties in obtaining primary tumor metaphases.

Methods and Results: We examined three CaP cell lines (LNCaP, DU145, PC-3) using sequential Giemsa banding and spectral karyotyping (SKY) to search for a common structural aberration or translocation breakpoint. No consistent rearrangement common to all three cell lines was detected. A clustering of centromeric translocation breakpoints was detected in chromosomes 4, 5, 6, 8, 11, 12, 14, and 15 in DU145 and PC-3. Both these lines were found to have karyotypes with a greater level of complexity than LNCaP.

Conclusion: The large number of structural aberrations present in DU145 and PC-3 implicate an underlying chromosomal instability and subsequent accumulation of cytogenetic alterations that confer a selective growth advantage. The high frequency of centromeric rearrangements in these lines indicates a potential role for mitotic irregularities associated with the centromere in CaP tumorigenesis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Haas GP, Sakr WA: Epidemiology of prostate cancer. CA Cancer J Clin 1997;47:273–287

    Article  PubMed  CAS  Google Scholar 

  2. Weinberg R: How cancer arises. Sci Am 1996;275: 62-70

    Article  PubMed  CAS  Google Scholar 

  3. Rowley JD: The critical role of chromosome translocations in human leukemias. Annu Rev Genet 1998;32: 495–519

    Article  PubMed  CAS  Google Scholar 

  4. Ladanyi M: The emerging molecular genetics of sarcoma translocations. Diagn Mol Pathol 1995;4: 162–173

    Article  PubMed  CAS  Google Scholar 

  5. Webb HD, Hawkins AL, Griffin CA: Cytogenetic abnormalities are frequent in uncultured prostate cancer cells. Cancer Genet Cytogenet 1996,88: 126–132

    Article  PubMed  CAS  Google Scholar 

  6. Konig JJ, Teubel W, van Dongen JW, Hagemeijer A, Romijn JC, Schroder FH: Tissue culture loss of aneuploid cells from carcinomas of the prostate. Genes Chromosomes Cancer 1993;8: 22–27

    Article  PubMed  CAS  Google Scholar 

  7. Ketter R, Zwergel T, Romanakis K, et al.: Selection toward diploid cells in prostatic carcinoma-derived cell cultures. Prostate 1996;28: 364–371

    Article  PubMed  CAS  Google Scholar 

  8. Chopra DP, Sarkar FH, Grignon DJ, Sakr WA, Mohammed A, Waghray A: Growth of human nondiploid primary prostate tumor epithelial cells in vitro. Cancer Res 1997;57: 3688–3692

    PubMed  CAS  Google Scholar 

  9. Limon J, Lundgren R, Elfving P, et al.: An improved technique for short-term culturing of human prostatic adenocarcinoma tissue for cytogenetic analysis. Cancer Genet Cytogenet 1990;46: 191–199

    Article  PubMed  CAS  Google Scholar 

  10. Peehl DM, Sellers RG, Wong ST: Defined medium for normal adult human prostatic stromal cells. In Vitro Cell Dev Biol Anim 1998;34: 555–560

    Article  PubMed  CAS  Google Scholar 

  11. Szucs S, Zitzelsberger H, Breul J, Bauchinger M, Hofler H: Two-phase short-term culture method for cytogenetic investigations from human prostate carcinoma. Prostate 1994;25: 225–235

    Article  PubMed  CAS  Google Scholar 

  12. Zwergel T, Kakirman H, Schorr H, Wullich B, Unteregger G: A new serial transfer expiant cell culture system for human prostatic cancer tissues preventing selection toward diploid cells. Cancer Genet Cytogenet 1998;101: 16–23

    Article  PubMed  CAS  Google Scholar 

  13. Arps S, Rodewald A, Schmalenberger B, Carl P, Bressel M, Kastendieck H: Cytogenetic survey of 32 cancers of the prostate. Cancer Genet Cytogenet 1993;66: 93–99

    Article  PubMed  CAS  Google Scholar 

  14. Micale MA, Sanford JS, Powell IJ, Sakr WA, Wolman SR: Defining the extent and nature of cytogenetic events in prostatic adenocarcinoma: Paraffin FISH vs metaphase analysis. Cancer Genet Cytogenet 1993;69: 7–12

    Article  PubMed  CAS  Google Scholar 

  15. Zitzelsberger H, Szucs S, Robens E, Weier HU, Hofler H, Bauchinger M: Combined cytogenetic and molecular genetic analyses of fifty-nine untreated human prostate carcinomas. Cancer Genet Cytogenet 1996;90: 37–44

    Article  PubMed  CAS  Google Scholar 

  16. Horoszewicz JS, Leong SS, Kawinski E, et al.: LNCaP model of human prostatic carcinoma. Cancer Res 1983;43: 1809–1818

    PubMed  CAS  Google Scholar 

  17. Gibas Z, Becher R, Kawinski E, Horoszewicz J, Sandberg AA: A high-resolution study of chromosome changes in a human prostatic carcinoma cell line (LNCaP). Cancer Genet Cytogenet 1984;11: 399-404

    Article  PubMed  CAS  Google Scholar 

  18. Stone KR, Mickey DD, Wunderli H, Mickey GH, Paulson DF: Isolation of a human prostate carcinoma cell line (DU 145). Int J Cancer 1978;21: 274–281

    Article  PubMed  CAS  Google Scholar 

  19. Kaighn ME, Narayan KS, Ohnuki Y, Lechner JF, Jones LW: Establishment and characterization of a human prostatic carcinoma cell line (PC-3). Invest Urol 1979;17: 16–23

    PubMed  CAS  Google Scholar 

  20. Veronese ML, Bullrich F, Negrini M, Croce CM: The t(6;16)(p21;q22) chromosome translocation in the LNCaP prostate carcinoma cell line results in a tpc/hpr fusion gene. Cancer Res 1996;56: 728–732

    PubMed  CAS  Google Scholar 

  21. Bernardino J, Bourgeois CA, Muleris M, Dutrillaux AM, Malfoy B, Dutrillaux B: Characterization of chromosome changes in two human prostatic carcinoma cell lines (PC-3 and DU145) using chromosome painting and comparative genomic hybridization. Cancer Genet Cytogenet 1997;96: 123–128

    Article  PubMed  CAS  Google Scholar 

  22. Schrock E, du Manoir S, Veldman T, et al.: Multicolor spectral karyotyping of human chromosomes. Science 1996;273: 494–497

    Article  PubMed  CAS  Google Scholar 

  23. Horoszewicz JS, Leong SS, Chu TM, et al.: The LNCaP cell line—A new model for studies on human prostatic carcinoma. Prog Clin Biol Res 1980; 37: 115–132

    PubMed  CAS  Google Scholar 

  24. Gustashaw KM: Chromosome stains. In Barch MJ, Knutsen T, Spurbeck JL: The AGT cytogenetics laboratory manual, 3. Lippincott-Raven, Philadelphia, 1997, pp. 259-324

  25. Veldman T, Vignon C, Schrock E, Rowley JD, Ried T: Hidden chromosome abnormalities in haematological malignancies detected by multicolour spectral karyotyping. Nat Genet 1997; 15: 406–410

    Article  PubMed  CAS  Google Scholar 

  26. Garini Y, Macville M, Manoir S, et al.: Spectral karyotyping. Bioimaging 1996;4: 65–72

    Article  Google Scholar 

  27. Mitelman F: ISCN (1995): International system for human cytogenetic nomenclature. Karger, New York, 1995

  28. Padilla-Nash HM, Nash WG, Padilla GM, et al.: Molecular cytogenetic analysis of the bladder carcinoma cell line BK-10 by spectral karyotyping. Genes Chromosomes Cancer 1999;25: 53–59

    Article  PubMed  CAS  Google Scholar 

  29. Allen RJ, Smith SD, Moldwin RL, et al.: Establishment and characterization of a megakaryoblast cell line with amplification of MLL.Leukemia 1998; 12: 1119-1127

    Article  PubMed  CAS  Google Scholar 

  30. Ford S, Gray IC, Spurr NK: Rearrangement of the long arm of chromosome 10 in the prostate adeno-carcinoma cell line LNCaP. Cancer Genet Cytogenet 1998;102: 6–11

    Article  PubMed  CAS  Google Scholar 

  31. Brothman AR, Maxwell TM, Cui J, Deubler DA, Zhu XL: Chromosomal clues to the development of prostate tumors. Prostate 1999;38: 303–312

    Article  PubMed  CAS  Google Scholar 

  32. Camby I, Etievant C, Petein M, et al.: Influence of culture media on the morphological differentiation of the PC-3 and DU145 prostatic neoplastic cell lines. Prostate 1994;24: 187–196

    Article  PubMed  CAS  Google Scholar 

  33. Nupponen NN, Hyytinen ER, Kallioniemi AH, Visakorpi T: Genetic alterations in prostate cancer cell lines detected by comparative genomic hybridization. Cancer Genet Cytogenet 1998;101: 53–57

    Article  PubMed  CAS  Google Scholar 

  34. Vig BK, Sternes KL, Paweletz N: Centromere structure and function in neoplasia. Cancer Genet Cytogenet 1989;43: 151–178

    Article  PubMed  CAS  Google Scholar 

  35. Broccoli D, Paweletz N, Vig BK: Sequence of centromere separation: Characterization of multicentric chromosomes in a rat cell line. Chromosoma 1989; 98: 13–22

    Article  PubMed  CAS  Google Scholar 

  36. Kaiser-Rogers K, Rao K: Structural chromosome rearrangements. In Gersen SL, Keagle MB: The principles of clinical cytogenetics, Humana Press, Totowa, 1999, pp. 191-228

  37. Chan GK, Schaar BT, Yen TJ: Characterization of the kinetochore binding domain of CENP-E reveals interactions with the kinetochore proteins CENP-F and hBUBR 1. J Cell Biol 1998; 143: 49–63

    Article  PubMed  CAS  Google Scholar 

  38. Faulkner NE, Vig B, Echeverri CJ, Wordeman L, Vallee RB: Localization of motor-related proteins and associated complexes to active, but not inactive, centromeres. Hum Mol Genet 1998;7: 671–677

    Article  PubMed  CAS  Google Scholar 

  39. Cahill DP, da Costa LT, Carson-Walter EB, Kinzler KW, Vogelstein B, Lengauer C: Characterization of MAD2B and other mitotic spindle checkpoint genes. Genomics 1999;58: 181–187

    Article  PubMed  CAS  Google Scholar 

  40. Sawyer JR, Tricot G, Mattox S, Jagannath S, Barlogie B: Jumping translocations of chromosome 1q in multiple myeloma: Evidence for a mechanism involving decondensation of pericentromeric heterochromatin. Blood 1998;91: 1732–1741

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Ontario Cancer Institute, University Health Network, 610 University Ave, Toronto, Ontario, M5G 2M9, Canada

    B. Beheshti BSc, J. Karaskova MSc, P. C. Park PhD, J. A. Squire PhD & B. G. Beatty PhD

  2. Departments of Laboratory Medicine and Pathobiology and Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, Canada

    B. Beheshti BSc, P. C. Park PhD, J. A. Squire PhD & B. G. Beatty PhD

Authors
  1. B. Beheshti BSc
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. Karaskova MSc
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P. C. Park PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. A. Squire PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. B. G. Beatty PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J. A. Squire PhD.

Additional information

Supported in part by the US Army Medical Research and Materiel Command Prostate Cancer Research Program; and a grant from the American Foundation for Urologic Diseases/ American Urologic Association Research Scholar Program and Imclone Systems, Inc (P.C.P.)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Beheshti, B., Karaskova, J., Park, P.C. et al. Identification of a High Frequency of Chromosomal Rearrangements in the Centromeric Regions of Prostate Cancer Cell Lines by Sequential Giemsa Banding and Spectral Karyotyping. Molecular Diagnosis 5, 23–32 (2000). https://doi.org/10.1007/BF03262019

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03262019

Key words

Search

Navigation