Document Detail

Inhibition of tumorigenicity of the teratoma PC cell line by transfection with antisense cDNA for PC cell-derived growth factor (PCDGF, epithelin/granulin precursor).
MedLine Citation:
PMID:  9826678     Owner:  NLM     Status:  MEDLINE    
The PC cell line is a highly tumorigenic, insulin-independent, teratoma-derived cell line isolated from the nontumorigenic, insulin-dependent 1246 cell line. Studies of the PC cell growth properties have led to the purification of an 88-kDa secreted glycoprotein called PC cell-derived growth factor (PCDGF), which has been shown to stimulate the growth of PC cells as well as 3T3 fibroblasts. Sequencing of PCDGF cDNA demonstrated its identity to the precursor of a family of 6-kDa double-cysteine-rich polypeptides called epithelins or granulins (epithelin/granulin precursor). Since PCDGF was isolated from highly tumorigenic cells, its level of expression was examined in PC cells as well as in nontumorigenic and moderately tumorigenic cells from which PC cells were derived. Northern blot and Western blot analyses indicate that the levels of PCDGF mRNA and protein were very low in the nontumorigenic cells and increased in tumorigenic cell lines in a positive correlation with their tumorigenic properties. Experiments were performed to determine whether the autocrine production of PCDGF was involved in the tumorigenicity of PC cells. For this purpose, we examined the in vivo growth properties in syngeneic C3H mice of PC cells where PCDGF expression had been inhibited by transfection of antisense PCDGF cDNA. The results show that inhibition of PCDGF expression resulted in a dramatic inhibition of tumorigenicity of the transfected cells when compared with empty-vector control cells. These data demonstrate the importance in tumor formation of overexpression of the novel growth factor PCDGF.
H Zhang; G Serrero
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  95     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  1998 Nov 
Date Detail:
Created Date:  1998-12-28     Completed Date:  1998-12-28     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  14202-7     Citation Subset:  IM    
Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy and Program of Oncology, Marlene and Stewart Greenebaum Cancer Center of the University of Maryland, Baltimore, MD 21201-1180, USA.
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MeSH Terms
Cell Line, Transformed
DNA, Antisense*
DNA, Complementary
Glycoproteins / biosynthesis,  genetics*,  isolation & purification
Growth Substances / biosynthesis,  genetics*,  isolation & purification
Insulin / physiology
Intercellular Signaling Peptides and Proteins*
Mice, Inbred C3H
Protein Precursors / genetics
Teratoma / genetics,  pathology*
Transcription, Genetic*
Transfection / methods
Tumor Cells, Cultured
Grant Support
Reg. No./Substance:
0/DNA, Antisense; 0/DNA, Complementary; 0/Glycoproteins; 0/Growth Substances; 0/Intercellular Signaling Peptides and Proteins; 0/Protein Precursors; 11061-68-0/Insulin; 134710-81-9/granulin precursor protein

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