Polyploid formation via chromosome duplication induced by CTP:phosphocholine cytidylyltransferase deficiency and Bcl-2 overexpression: identification of two novel endogenous factors.
Polyploidy is a profound phenotype found in tumors and its mechanism is unknown. We report here that when B-cell lymphoma gene-2 (Bcl-2) was overexpressed in a Chinese hamster ovary cell line that was deficient in CTP:phosphocholine cytidylyltransferase (CT), cellular DNA content doubled. The higher DNA content was due to a permanent conversion from diploid cells to tetraploid cells. The mechanism of polyploid formation could be attributed to the duplication of 18 parental chromosomes. The rate of conversion from diploid to tetraploid was Bcl-2 dose dependent. The diploid genome was not affected by Bcl-2 expression or by CT deficiency alone. Endogenous CT or expression of recombinant rat liver CTalpha prior to Bcl-2 expression prevented the formation of polyploid cells. This conversion was irreversible even when both initiating factors were removed. In this study, we have identified Bcl-2 as a positive regulator and CTalpha as a negative regulator of polyploid formation.
Shen
You-Jun
YJ
Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC 27599-7525, USA.
DeLong
Cynthia J
CJ
Tercé
Francois
F
Kute
Timothy
T
Willingham
Mark C
MC
Pettenati
Mark J
MJ
Cui
Zheng
Z
D000818:Animals; D016466:CHO Cells; D048429:Cell Size; D019916:Choline-Phosphate Cytidylyltransferase / Q000172:deficiency* / Q000235:genetics; D002871:Chromosome Banding; D033481:Chromosomes, Mammalian / Q000235:genetics*; D006224:Cricetinae; D003412:Cricetulus; D004261:DNA Replication; D004171:Diploidy; D006801:Humans; D051379:Mice; D011123:Polyploidy; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics
D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D019916:Choline-Phosphate Cytidylyltransferase