1993 Volume 35 Issue 6 Pages 505-519
The HSG cell line is a intercalated ductal adenocarcinoma cell line established from a human salivary gland and it proliferates autonomously mediated by an epidermal growth factor (EGF)-like molecule and an EGF receptor. HSG cells are pluripotent and are differentiated into cells having various phenotypes by differentiation inducers. In the present study, the effects of dibutyryl cyclic AMP (dB-cAMP) on the proliferation and the differentiation of HSG cells were investigated in respect of autocrine growth.
Treatment of HSG cells with dB-cAMP induced dose-dependent changes in cell morphology namely HSG cells became spindles and formed long cytoplasmic processes. The appearances of S-100 protein and myosin in the dB-cAMP treated cells were observed while no expression occurred in untreated cells, suggesting that dB-cAMP differentiated HSG cells into myoepithelial-like cells. The cell number and [3H] thymidine incorporation into DNA were decreased. The expression of the c-fos protein, which is a product of proto-oncogene, was observed in the untreated HSG cells constitutively, and became undetectable by the treatment of dB-cAMP. The treatment of dB-cAMP resulted in a decrease of the level of the EGF receptor, whereas it had no effect on the level of the EGF-like molecule. Furthermore, the dB-cAMP treatment of HSG cells delayed the G2/M phase in the cell cycle. These findings indicate that dB-cAMP induces HSG cells to differentiate into cells having a myoepithelial phenotype and that it also exerts a growth inhibitory effect on HSG cells. It was suggested that the suppression of the signal transmittance by the decreased level of the EGF receptor in the autocrine proliferation of HSG cells mediated by the EGF-like molecule and its receptor and the disappearance of the c-fos protein were involved in this growth inhibition.
