A cyclized peptide derived from alpha fetoprotein inhibits the proliferation of ER-positive canine mammary cancer cells.
The effects of estradiol (E2) and of an AFP-derived cyclized peptide (cP) on the proliferation of primary cultures of cancer cells isolated from spontaneous canine mammary tumors were studied. The cellular response to E2 and cP was related to the expression of estradiol receptor (isoforms alpha and beta). In ER-positive cells, 2 nM estradiol increased cell proliferation and the phosphorylation of ERK1/2; 2 microg/ml cP inhibited all these effects. Estradiol also increased HER2 immunoreactivity in ER-positive cells, an effect that was reverted to its basal values by cP. Estradiol stimulated in these cells the release of MMP2 and MMP9 and the shedding of HB-EGF, effects that the cP did not affect. ER-negative cells were refractory to estradiol or cP. All canine mammary tumor cells in culture responded to treatments analogously to human mammary cancer cells. Our results support the proposal of cP as a new, potentially effective therapeutic agent for the management of mammary cancer.
Laboratorios de Nutrición y Regulación Metabólica, Sección Ultraestructuras, INTA-Universidad de Chile, Santiago 7830489, Chile.
Cristian Gabriel
CG
Torres
Ana María
AM
Pino
Walter Daniel
WD
Sierralta
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D004285:Dogs; D004815:Epidermal Growth Factor / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism; D004965:Estrogen Antagonists / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000187:drug effects / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D015674:Mammary Neoplasms, Animal / Q000378:metabolism / Q000473:pathology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009367:Neoplasm Staging; D010456:Peptides, Cyclic / Q000494:pharmacology*; D010766:Phosphorylation; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013629:Tamoxifen / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D000509:alpha-Fetoproteins / Q000494:pharmacology*
D000970:Antineoplastic Agents; D004815:Epidermal Growth Factor; D004958:Estradiol; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D010456:Peptides, Cyclic; D018719:Erb-b2 Receptor Tyrosine Kinases; D013629:Tamoxifen; D000509:alpha-Fetoproteins; C587883:HBEGF protein, human