PC Cell-Derived Growth Factor Mediates Tamoxifen Resistance and Promotes Tumor Growth of Human Breast Cancer Cells
| Autor: | Jun Hayashi, Wisit Tangkeangsirisin, Ginette Serrero |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Cancer Research
medicine.medical_specialty medicine.drug_class medicine.medical_treatment Apoptosis Breast Neoplasms Biology medicine.disease_cause Mice chemistry.chemical_compound Internal medicine medicine Animals Humans Growth Substances skin and connective tissue diseases Glycoproteins Neovascularization Pathologic Growth factor Cancer medicine.disease Antiestrogen Vascular endothelial growth factor Tamoxifen Endocrinology Proto-Oncogene Proteins c-bcl-2 Oncology chemistry Drug Resistance Neoplasm Estrogen Cancer cell Intercellular Signaling Peptides and Proteins Female Poly(ADP-ribose) Polymerases Carcinogenesis Cell Division medicine.drug |
| Zdroj: | Cancer Research. 64:1737-1743 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | PC cell-derived growth factor, also known as progranulin, is an Mr 88,000 growth factor (referred as PCDGF/GP88) overexpressed in human breast cancer. Antisense inhibition of PCDGF/GP88 expression in MDA-MB-468 cells inhibited tumor formation in nude mice. In estrogen receptor-positive cells, PCDGF/GP88 was expressed in response to estradiol and shown to mediate its mitogenic effect. Pathologic studies indicated that PCDGF/GP88 was expressed in 80% of invasive ductal carcinomas in correlation with parameters of poor prognosis. In the present article, the relationship between PCDGF/GP88 expression and tamoxifen resistance was examined in MCF-7 cells. PCDGF/GP88 overexpression rendered MCF-7 cells able to proliferate in the absence of estrogen and in the presence of tamoxifen. The PCDGF/GP88-overexpressing cells formed tumors in ovariectomized nude mice in the absence of estradiol and in its presence, in contrast to MCF-7 cells. Tumor growth of the overexpressing cells was increased significantly when the mice were treated with tamoxifen. PCDGF/GP88 blocked tamoxifen-induced apoptosis by preventing down-regulation of bcl-2 expression and poly(ADP-ribose) polymerase cleavage. In addition, PCDGF/GP88-overexpressing cells presented higher level of the angiogenic factors vascular endothelial growth factor and angiopoietin-1 than MCF-7 control cells. Tamoxifen treatment additionally increased the level of vascular endothelial growth factor. These studies suggest that PCDGF/GP88 plays a critical role in breast cancer tumorigenesis and in the transition to estrogen independence and tamoxifen resistance, a hallmark of poor prognosis. On the basis of the in vivo studies, it is postulated that tamoxifen treatment of patients with estrogen receptor-positive breast tumors overexpressing PCDGF/GP88 could have adverse clinical consequences. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|