Spontaneous regression of cutaneous melanoma in sinclair swine is associated with defective telomerase activity and extensive telomere erosion.

  • Authors:
    • S Pathak
    • A S Multani
    • D J McConkey
    • A S Imam
    • M S Amoss
  • View Affiliations

  • Published online on: December 1, 2000     https://doi.org/10.3892/ijo.17.6.1219
  • Pages: 1219-1243
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Abstract

Recently we proposed the hypothesis that extensive telomeric association of chromosomes is an early manifestation of cell death and asked whether there are extensive telomeric associations present in metaphases of the spontaneously regressing Sinclair swine cutaneous melanoma (SSCM). Our results indicate that early passage SSCMs, in the accelerated growth phase, do not show telomeric associations but do have numerical and other specific structural abnormalities. However, the same melanoma cell lines at late passages or melanomas obtained from middle- and old-aged Sinclair swine show extensive telomeric associations in the form of dicentric, multicentric, and ring configurations. Such abnormal structures are present mostly in metaphases that are hyperploids. Increasing frequencies of apoptotic bodies were also observed in higher passage tumor cell lines obtained from younger animals or in melanomas obtained from older animals. The polymerase chain reaction (PCR)-based telomeric repeat amplification protocol (TRAP) assay shows no detectable telomerase activity in any of these regressing swine melanoma cell lines, neither in normal swine skin fibroblasts nor in nevi. However, the fetal swine (i.e., non-regressing) melanoma cells show telomerase activity. Fluorescence in situ hybridization (FISH) results using the commercially available human telomeric repeat DNA probe indicate a reduction of telomeric signals in metaphase and interphase cells of regressing melanomas. From these observations we conclude that spontaneous regression of SSCM is associated with the loss of telomerase activity and a reduction of telomeric repeats that results in the formation of multicentric and ring configurations. Such abnormal chromosome configurations are lost, following the breakage-fusion-bridge-cycles, and result in extensive DNA fragmentation, as shown by laddering experiments, and, finally, cell death.

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Dec 2000
Volume 17 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Pathak S, Multani A, McConkey D, Imam A and Amoss M: Spontaneous regression of cutaneous melanoma in sinclair swine is associated with defective telomerase activity and extensive telomere erosion.. Int J Oncol 17: 1219-1243, 2000.
APA
Pathak, S., Multani, A., McConkey, D., Imam, A., & Amoss, M. (2000). Spontaneous regression of cutaneous melanoma in sinclair swine is associated with defective telomerase activity and extensive telomere erosion.. International Journal of Oncology, 17, 1219-1243. https://doi.org/10.3892/ijo.17.6.1219
MLA
Pathak, S., Multani, A., McConkey, D., Imam, A., Amoss, M."Spontaneous regression of cutaneous melanoma in sinclair swine is associated with defective telomerase activity and extensive telomere erosion.". International Journal of Oncology 17.6 (2000): 1219-1243.
Chicago
Pathak, S., Multani, A., McConkey, D., Imam, A., Amoss, M."Spontaneous regression of cutaneous melanoma in sinclair swine is associated with defective telomerase activity and extensive telomere erosion.". International Journal of Oncology 17, no. 6 (2000): 1219-1243. https://doi.org/10.3892/ijo.17.6.1219