Transfected MCF-7 cells as a model for breast-cancer progression.
The MCF-7 human breast carcinoma cell line has been used as a recipient for eukaryotic plasmid expression vectors to determine the effects of growth factor and growth factor receptor overexpression on the estrogen-dependent, antiestrogen sensitive and poorly metastatic phenotypes exhibited by this line. Overexpression of some members of the erbB family of ligands and receptors were found to have some effects on these phenotypes. However, only when two members of the fibroblast growth factor family, FGF-1 and FGF-4, were overexpressed was progressive in vivo growth observed is either ovariectomized nude mice without estrogen supplementation or in mice that received tamoxifen treatment. FGF transfected cells also exhibited an increased ability to form micrometastases. The implications of these results with regard to the possible role of the paracrine and autocrine effects of angiogenic growth factor production in breast cancer progression are discussed.
Kern
F G
FG
Lombardi Cancer Research Center, Georgetown University Medical Center, Washington, DC 20007.
McLeskey
S W
SW
Zhang
L
L
Kurebayashi
J
J
Liu
Y
Y
Ding
I Y
IY
Kharbanda
S
S
Chen
D
D
Miller
D
D
Cullen
K
K
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology*; D043925:Angiogenesis Inducing Agents / Q000502:physiology; D000818:Animals; D001943:Breast Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D018450:Disease Progression; D004351:Drug Resistance; D016228:Endothelial Growth Factors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D004967:Estrogens; D005260:Female; D005346:Fibroblast Growth Factors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008222:Lymphokines / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009368:Neoplasm Transplantation; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics / Q000473:pathology*; D017468:Receptors, Fibroblast Growth Factor / Q000096:biosynthesis / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D013629:Tamoxifen / Q000494:pharmacology / Q000627:therapeutic use; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000637:transplantation; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D043925:Angiogenesis Inducing Agents; D016228:Endothelial Growth Factors; D004967:Estrogens; D008222:Lymphokines; D009363:Neoplasm Proteins; D017468:Receptors, Fibroblast Growth Factor; D011993:Recombinant Fusion Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D013629:Tamoxifen; D005346:Fibroblast Growth Factors