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Effect on tumorigenicity and metastasis of transfection of a diploid benign rat mammary epithelial cell line with DNA corresponding to the mRNA for basic fibroblast growth factor
Author(s) -
Davies Barry R.,
Fernig David G.,
Barraclough Roger,
Rudland Philip S.
Publication year - 1996
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19960103)65:1<104::aid-ijc18>3.0.co;2-g
Subject(s) - transfection , basic fibroblast growth factor , paracrine signalling , biology , autocrine signalling , cell culture , metastasis , growth factor , carcinogenesis , microbiology and biotechnology , cell growth , mammary gland , endocrinology , cancer research , medicine , receptor , cancer , gene , biochemistry , genetics , breast cancer
To examine the potential role of fibroblast growth factors (FGF) in tumorigenesis and metastasis, plasmid constructs containing the human basic FGF (bFGF) gene, with or without fusion to a secretory signal peptide (IgbFGF), were transfected into the diploid rat mammary epithelial cell line Rama 37. All transfectants possessed multiple copies of the transfected cDNA, which was expressed as the corresponding mRNA and the protein. The amount of bFGF protein was usually greater than the bFGF growth‐stimulatory activity that could be recovered from the transfected cells. Nevertheless, the amount of bFGF growth‐stimulatory activity secreted by the IgbFGF transfectants (0.08–0.8 ng/ml/24 hr) was sufficient to induce growth in responsive cells. However, the transfectants themselves were refractory to stimulation by exogenously added bFGF, despite possessing a small number of high‐affinity receptors for bFGF. When the bFGF or the IgbFGF transfectants were inoculated into the mammary fat pads of syngeneic rats, the tumour incidence was low (0–50%). However, when cells cultured from these tumours were inoculated into the fat pad of syngeneic rats, the tumour incidence was 100%. Tumours were in all cases benign and no metastases were observed. Our results suggest that the role of bFGF in metastasis is not simply one of autocrine/paracrine stimulation of cell growth and that other events may also be required. © 1996 Wiley‐Liss, Inc.