PMID- 15023530
OWN - NLM
STAT- MEDLINE
DCOM- 20040505
LR  - 20171116
IS  - 0014-4827 (Print)
IS  - 0014-4827 (Linking)
VI  - 294
IP  - 2
DP  - 2004 Apr 1
TI  - Immortalization in a normal foreskin fibroblast culture following transduction of 
      cyclin A2 or cdk1 genes in retroviral vectors.
PG  - 406-19
AB  - Human diploid fibroblasts (HDF) rarely, if ever, undergo spontaneous 
      transformation to an immortalized cell type. Here we report the immortalization 
      of an HDF cell line following transduction with cyclin A2 or cdk1 human genes via 
      retroviral vectors. Fluorescence in situ hybridization (FISH) studies using the 
      retroviral vector as a probe indicate that these cell lines are monoclonal. No 
      telomerase activity could be detected in these cell lines, and the telomere 
      length in the immortalized cells was observed to be 10-20 kb longer than that in 
      low-passage cells from the parental fibroblast line. Cytogenetic studies revealed 
      that the immortal lines share common chromosomal aberrations. FISH studies with a 
      probe for p53 revealed loss of one copy of this gene which was associated with 
      reduced steady-state levels of both p53 and p53-regulated p21(WAF1/Sdi1/CIP1) 
      messages in both quiescent and proliferating immortalized cultures relative to 
      the parental cells. Additional FISH studies with probes for p16(INK4a) and Rb, 
      carried out after the immortalized cells proliferated in excess of 100 population 
      doublings, also revealed loss of one copy of these genes in both cell lines. 
      These cell lines, together with the well-characterized parental cells, could 
      provide useful research material for the study of the mechanisms of 
      immortalization and of regulation of proliferative senescence in HDF.
FAU - Luo, Ping
AU  - Luo P
AD  - Department of Pathology, University of Washington Seattle, Seattle, WA 98195, 
      USA.
FAU - Tresini, Maria
AU  - Tresini M
FAU - Cristofalo, Vincent
AU  - Cristofalo V
FAU - Chen, Xiaoqin
AU  - Chen X
FAU - Saulewicz, Anthony
AU  - Saulewicz A
FAU - Gray, Matthew D
AU  - Gray MD
FAU - Banker, Deborah E
AU  - Banker DE
FAU - Klingelhutz, Aloysius L
AU  - Klingelhutz AL
FAU - Ohtsubo, Motoaki
AU  - Ohtsubo M
FAU - Takihara, Yoshihiro
AU  - Takihara Y
FAU - Norwood, Thomas H
AU  - Norwood TH
LA  - eng
GR  - 1P30 AG13280/AG/NIA NIH HHS/United States
GR  - P01 AG01751/AG/NIA 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  - United States
TA  - Exp Cell Res
JT  - Experimental cell research
JID - 0373226
RN  - 0 (CCNA2 protein, human)
RN  - 0 (CDKN1A protein, human)
RN  - 0 (Cyclin A)
RN  - 0 (Cyclin A2)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p16)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 0 (Cyclins)
RN  - 0 (Retinoblastoma Protein)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - EC 2.7.11.22 (CDC2 Protein Kinase)
RN  - EC 2.7.7.49 (Telomerase)
SB  - IM
MH  - CDC2 Protein Kinase/biosynthesis/*genetics
MH  - Cell Division/genetics
MH  - Cell Line, Transformed
MH  - Cellular Senescence/*genetics
MH  - Chromosome Aberrations
MH  - Clone Cells/metabolism
MH  - Cyclin A/biosynthesis/*genetics
MH  - Cyclin A2
MH  - Cyclin-Dependent Kinase Inhibitor p16/genetics
MH  - Cyclin-Dependent Kinase Inhibitor p21
MH  - Cyclins/genetics
MH  - Fibroblasts/enzymology/*metabolism
MH  - Genetic Vectors/genetics
MH  - Humans
MH  - Infant, Newborn
MH  - Loss of Heterozygosity/genetics
MH  - Male
MH  - Retinoblastoma Protein/genetics
MH  - Retroviridae/genetics
MH  - Telomerase/metabolism
MH  - Transduction, Genetic/*methods
MH  - Tumor Suppressor Protein p53/genetics
EDAT- 2004/03/17 05:00
MHDA- 2004/05/07 05:00
CRDT- 2004/03/17 05:00
PHST- 2003/07/09 00:00 [received]
PHST- 2003/11/17 00:00 [revised]
PHST- 2004/03/17 05:00 [pubmed]
PHST- 2004/05/07 05:00 [medline]
PHST- 2004/03/17 05:00 [entrez]
AID - S0014482703006372 [pii]
AID - 10.1016/j.yexcr.2003.11.030 [doi]
PST - ppublish
SO  - Exp Cell Res. 2004 Apr 1;294(2):406-19. doi: 10.1016/j.yexcr.2003.11.030.