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Effect of Growth Factors on Proliferation of Normal, Borderline, and Malignant Breast Epithelial Cells

Experimental and Molecular Pathology
Publication Date
DOI: 10.1006/exmp.1999.2294
  • Biology
  • Medicine


Abstract Growth factors play an important role in the development and growth regulation of normal breast. They are also known to be autocrine or paracrine stimulators of breast cancer cells. However, their role on cells of proliferative breast disease has not been studied so far. This study was undertaken to quantitate the proliferative effect of various growth factors on “normal,” borderline, and malignant breast epithelial cells. For this purpose, epithelial cell lines of histologically normal human breast and histologically proven proliferative breast diseases were established. Cell lines MCF-7 and T47D were used as malignant cells. The growth factors under study include epidermal growth factor, fibroblast growth factors acidic and basic, platelet-derived growth factor, and insulin-like growth factors 1 (IGF-1) and 2 (IGF-2). Their proliferative effect was determined by incubating the cells with growth factors for 24 h after achieving basal conditions in serum-free medium for 72 h, followed by quantitating the S-phase fraction by flow cytometry. All of the growth factors were found to be capable of inducing cellular proliferation on the entire range of mammary epithelia. Epidermal growth factor was consistently found to be a potent mitogen. Fibroblast growth factor acidic had a higher effect compared to fibroblast growth factor basic in inducing the cells to move from G 0/G 1 to S-phase. Platelet-derived growth factor had a moderate proliferative response. In the family of insulin-like growth factors, IGF-1 was the dominant mitogen for normal cells and IGF-2 was the dominant proliferative stimulus for the cell line MCF-7. In the cell lines of proliferative breast disease and T47D, both were at par as mitogenic agents. These results suggest that the cells of proliferative breast disease develop some of the biological characteristics of malignancy.

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