MCF-7 breast carcinoma cells overexpressing FGF-1 form vascularized, metastatic tumors in ovariectomized or tamoxifen-treated nude mice.
FGF-1 is expressed in a high proportion of breast tumors. While overexpression of FGF-4 in the MCF-7 breast carcinoma cell line confers the ability to form spontaneously metastasizing tumors in ovariectomized nude mice without estrogen supplementation and in mice that receive tamoxifen pellets, the response of a cell to individual FGFs can be controlled at multiple levels, and the significance of FGF-1 expression in human breast tumors is uncertain. To study the role of FGF-1, MCF-7 human breast cancer carcinoma cells, previously transfected with bacterial beta-galactosidase, were retransfected with FGF-1 expression vectors. FGF-1 transfectants formed large, vascularized tumors in ovariectomized nude mice without estrogen supplementation as well as in mice that received tamoxifen pellets. Lymphatic and pulmonary micrometastases were detected as deposits of X-gal-stained cells as early as 17 days after cell inoculation whereas no metastases were detected in estrogen-supplemented mice bearing similar-sized control tumors. When compared with controls, both clonal and polyclonal populations of FGF-1 overexpressing cells exhibited increased anchorage-independent growth and decreased population doubling times in estrogen-depleted or 4-hydroxytamoxifen containing medium. These results suggest that FGF signaling may be important in the transition of breast cancer cells from hormone-dependent to hormone-independent and from nonmetastatic to metastatic.
Zhang
L
L
Lombardi Cancer Center, Department of Biochemistry and Molecular Biology, Georgetown University Medical Center, Washington, DC 20007, USA.
Kharbanda
S
S
Chen
D
D
Bullocks
J
J
Miller
D L
DL
Ding
I Y
IY
Hanfelt
J
J
McLeskey
S W
SW
Kern
F G
FG
D000818:Animals; D001943:Breast Neoplasms / Q000098:blood supply* / Q000473:pathology*; D002199:Capillary Permeability; D002277:Carcinoma / Q000098:blood supply* / Q000556:secondary*; D002448:Cell Adhesion; D002455:Cell Division / Q000187:drug effects; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D016220:Fibroblast Growth Factor 1 / Q000235:genetics / Q000378:metabolism*; D005822:Genetic Vectors; D006801:Humans; D008175:Lung Neoplasms / Q000556:secondary; D008207:Lymphatic Metastasis; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000209:etiology*; D010052:Ovariectomy; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology*; D014162:Transfection; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D004965:Estrogen Antagonists; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D013629:Tamoxifen; D016220:Fibroblast Growth Factor 1; D001616:beta-Galactosidase