Neoplastic transformation of human diploid fibroblasts after long-term serum starvation.
Serum starvation for several days has been considered as a positive effect on the efficiency of nuclear transfer using donor cells. The effects of longer period serum starvation are not clear while similar starvation might occur in vitro maintained cells (i.e. tissue engineering products) and in vivo such as ischemia of human tissues or organs. We found human dermis fibroblasts were transformed for about 70 days caused by serum starvation (0.5% serum). The transformed cells became round and had more than one nucleolus. In 0.5% serum medium they kept almost constant growth rate as the normal fibroblasts in 10% serum medium. Abnormal karyotype including aneuploidy and structural aberrations was observed. The transformed cells had high telomerase activities, in contrast, normal fibroblasts had no detectable telomerase activities. C-myc was up-regulated while cdk2, cyclin A, p21 were down in transformed cells. Cell transplantation into SCID nude mice confirmed that the cells had the capacity of forming solid tumors. The results indicated that long-term serum starvation could lead to cell chromosomal instability and transformation.
Zhang
Jingyu
J
Key Laboratory of Molecular and Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, No. 3 Nanyitiao, Zhongguancun, Beijing 100080, China.
Wang
Xia
X
Zhao
Yanhong
Y
Chen
Bing
B
Suo
Guangli
G
Dai
Jianwu
J
D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000235:genetics / Q000473:pathology*; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004171:Diploidy; D005260:Female; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007621:Karyotyping; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000378:metabolism; D013997:Time Factors; D014183:Transplantation, Heterologous
D018797:Cell Cycle Proteins; D016895:Culture Media, Serum-Free; D012333:RNA, Messenger; D019098:Telomerase