PMID- 11078808
OWN - NLM
STAT- MEDLINE
DCOM- 20010201
LR  - 20190605
IS  - 1019-6439 (Print)
IS  - 1019-6439 (Linking)
VI  - 17
IP  - 6
DP  - 2000 Dec
TI  - Spontaneous regression of cutaneous melanoma in sinclair swine is associated with 
      defective telomerase activity and extensive telomere erosion.
PG  - 1219-24
AB  - 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.
FAU - Pathak, S
AU  - Pathak S
AD  - Cellular Genetics Laboratory, M.D. Anderson Cancer Center, 1515 Holcombe 
      Boulevard, Houston, TX 77030, USA. spathak@notes.mdacc.tmc.edu
FAU - Multani, A S
AU  - Multani AS
FAU - McConkey, D J
AU  - McConkey DJ
FAU - Imam, A S
AU  - Imam AS
FAU - Amoss, M S Jr
AU  - Amoss MS Jr
LA  - eng
GR  - P01CA 49488/CA/NCI NIH HHS/United States
GR  - RRO 4999-01/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Greece
TA  - Int J Oncol
JT  - International journal of oncology
JID - 9306042
RN  - 0 (Neoplasm Proteins)
RN  - EC 2.7.7.49 (Telomerase)
SB  - IM
MH  - Animals
MH  - Apoptosis/*genetics
MH  - Chromosome Aberrations
MH  - DNA Fragmentation
MH  - G2 Phase
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Inbreeding
MH  - Melanoma/enzymology/genetics/pathology/*veterinary
MH  - Models, Animal
MH  - Models, Genetic
MH  - Neoplasm Proteins/*deficiency/genetics
MH  - Nevus, Pigmented/enzymology/genetics/pathology/veterinary
MH  - Polymerase Chain Reaction
MH  - Remission, Spontaneous
MH  - Skin Neoplasms/enzymology/genetics/pathology/*veterinary
MH  - Swine
MH  - Swine Diseases/enzymology/*pathology
MH  - Swine, Miniature
MH  - Telomerase/*deficiency/genetics
MH  - Telomere/*ultrastructure
EDAT- 2000/11/18 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/11/18 11:00
PHST- 2000/11/18 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/11/18 11:00 [entrez]
AID - 10.3892/ijo.17.6.1219 [doi]
PST - ppublish
SO  - Int J Oncol. 2000 Dec;17(6):1219-24. doi: 10.3892/ijo.17.6.1219.