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

Runqing Lu, Ginette Serrero

Research output: Contribution to journalReview article

100 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)3993-3998
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number8
StatePublished - Apr 11 2000

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Complementary DNA
Breast Neoplasms
Cell Line
Teratoma
granulin precursor protein
Intercellular Signaling Peptides and Proteins
Breast
Epithelial Cells
Neutralizing Antibodies
Tumor Burden
Estrogen Receptors
Northern Blotting
Transfection
Neoplasms
Estrogens
Western Blotting
Messenger RNA
Incidence
Growth

ASJC Scopus subject areas

  • General

Cite this

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title = "Inhibition of PC cell-derived growth factor (PCDGF, epithelin/granulin precursor) expression by antisense PCDGF cDNA transaction inhibits tumorigenicity of the human breast carcinoma cell line MDA-MB-468",
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.",
author = "Runqing Lu and Ginette Serrero",
year = "2000",
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T1 - Inhibition of PC cell-derived growth factor (PCDGF, epithelin/granulin precursor) expression by antisense PCDGF cDNA transaction inhibits tumorigenicity of the human breast carcinoma cell line MDA-MB-468

AU - Lu, Runqing

AU - Serrero, Ginette

PY - 2000/4/11

Y1 - 2000/4/11

N2 - 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.

AB - 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.

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