DOI: 10.1073/pnas.97.8.3993. Inhibition of PC cell-derived growth factor (PCDGF, epithelin/granulin precursor) expression by antisense PCDGF cDNA transfection inhibits tumorigenicity of the human breast carcinoma cell line MDA-MB-468

Inhibition of PC cell-derived growth factor (PCDGF, epithelin/granulin precursor) expression by antisense PCDGF cDNA transfection inhibits tumorigenicity of the human breast carcinoma cell line MDA-MB-468

10.1073/pnas.97.8.3993

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

PC-cell derived growth factor (PCDGF) is an 88-kDa growth factor originally purified from the highly tumorigenic teratoma PC cell line and corresponds to the epithelin/granulin precursor. In teratoma cells, PCDGF expression was shown to be essential for tumorigenicity. We have reported that PCDGF was expressed in estrogen receptor-positive (ER + ) human mammary epithelial cells in an estrogen-dependent fashion. In this study, we have investigated PCDGF expression in human mammary epithelial cell lines ranging from immortalized nontumorigenic cells to ER + and ER − breast carcinoma cells. Northern and Western blot analyses indicated that PCDGF mRNA and protein expression was low in nontumorigenic cells and increased in human breast carcinomas cell lines in a positive correlation with their tumorigenicity. Treatment of the ER − MDA-MB-468 cells with anti-PCDGF neutralizing antibody resulted in a dose-dependent inhibition of their proliferation, suggesting that secreted PCDGF acted as an autocrine growth factor for breast carcinoma cells. We then examined the in vitro and in vivo growth properties of MDA-MB-468 cells, where PCDGF expression had been inhibited by antisense PCDGF cDNA transfection. Inhibition of PCDGF expression resulted in a reduced proliferation rate in vitro and a 60–80% reduction in colony formation. Tumor formation in vivo was dramatically inhibited in antisense cells with a 90% inhibition of tumor incidence and tumor weight. These results demonstrate the importance of PCDGF overexpression for the proliferation and tumorigenicity of ER − breast carcinomas and suggest that PCDGF overexpression may play an important role in human breast cancer.

Bibliography

Lu, R., & Serrero, G. (2000). Inhibition of PC cell-derived growth factor (PCDGF, epithelin/granulin precursor) expression by antisense PCDGF cDNA transfection inhibits tumorigenicity of the human breast carcinoma cell line MDA-MB-468. Proceedings of the National Academy of Sciences, 97(8), 3993â3998.

Authors 2

Runqing Lu (first)
Ginette Serrero (additional)

References 42 Referenced 106

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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:40 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 5:11 p.m.)
Indexed	3 weeks, 6 days ago (Aug. 6, 2025, 9 a.m.)
Issued	25 years, 4 months ago (April 11, 2000)
Published	25 years, 4 months ago (April 11, 2000)
Published Online	25 years, 4 months ago (April 11, 2000)
Published Print	25 years, 4 months ago (April 11, 2000)

Funders 0

None

BibTeX

@article{Lu_2000, title={Inhibition of PC cell-derived growth factor (PCDGF, epithelin/granulin precursor) expression by antisense PCDGF cDNA transfection inhibits tumorigenicity of the human breast carcinoma cell line MDA-MB-468}, volume={97}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.97.8.3993}, DOI={10.1073/pnas.97.8.3993}, number={8}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Lu, Runqing and Serrero, Ginette}, year={2000}, month=apr, pages={3993–3998} }

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