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Response of different mammary epithelial cell lines to a mammary derived growth inhibitor (MDGI)
W Lehmann1, R Widmaier, P Langen
1Department of Cell Kinetics, Academy of Sciences of the GDR, Berlin-Buch.
Abstract:
MDGI, a 14.5-KDa protein, is a chemically defined growth inhibitor, which we have purified from lactating bovine mammary gland and characterized biologically in a mouse Ehrlich ascites mammary tumour (EAT) short term suspension culture. It has now been tested for its inhibitory activity on proliferation of four malignant mammary epithelial cell lines of human and mouse origin and normal human mammary epithelial cells. In all experiments, cells were brought to quiescence by serum or growth factor deprivation. Using [3H]TdR pulse labelling the effect of MDGI was measured on the restimulation of proliferation after medium change. MaTu and T47 D, human malignant mammary epithelial cell lines, as well as the mouse malignant mammary epithelial cell line mMaCa 20177 could be inhibited, whereas the human malignant mammary epithelial cell line MCF7 showed a slight stimulation. MDGI showed no activity on the residual DNA synthesis of all cell lines after starvation. Normal human mammary epithelial cells (HMEC) of different passages could also be inhibited. Their responsiveness seemed to be dependent on the number of passages. Cells from high passages (10-14) showed a higher sensitivity, which is also about 10 times higher than that of the malignant cell lines. Furthermore, growth factors like insulin, epidermal growth factor (EGF) and fetal calf serum (FCS), known to be potent antagonists to the MDGI activity in the EAT and, in the case of insulin, also in the MaTu culture (shown in the present study), do not abolish the inhibitory activity of MDGI on HMEC cells. These results demonstrate that the inhibitory activity of MDGI is not exclusively restricted to EAT cells studied so far.
Insights
Mammary-derived growth inhibitor (MDGI) inhibits proliferation in human and mouse malignant mammary epithelial cells and normal human mammary epithelial cells. MDGI
Area of Science:
- Biochemistry
- Cell Biology
- Oncology
Background:
- MDGI is a 14.5-KDa protein purified from bovine mammary glands.
- MDGI's inhibitory activity was previously characterized in mouse Ehrlich ascites mammary tumor (EAT) cells.
Purpose of the Study:
- To investigate MDGI's inhibitory activity on human and mouse malignant mammary epithelial cell lines.
- To assess MDGI's effect on normal human mammary epithelial cells (HMEC).
Main Methods:
- Cells were rendered quiescent via serum/growth factor deprivation.
- [3H]TdR pulse labeling measured proliferation restimulation.
- MDGI's activity was tested on four malignant and normal mammary epithelial cell lines.
Main Results:
- MDGI inhibited MaTu, T47D, and mMaCa 20177 cell lines.
- MCF7 cell line showed slight stimulation; no residual DNA synthesis inhibition was observed.
- Normal HMEC cells were inhibited, with higher sensitivity in later passages (10-14).
- Growth factors (insulin, EGF, FCS) did not abolish MDGI's inhibitory effect on HMEC.
Conclusions:
- MDGI exhibits inhibitory activity beyond EAT cells.
- MDGI affects both malignant and normal mammary epithelial cells.
- MDGI's activity on normal cells is potent and not fully antagonized by common growth factors.