EGF MODULATION OF THE RAS-RELATED RHOB GENE-EXPRESSION IN HUMAN BREAST-CANCER CELL-LINES

The mRNA levels of the ras-related human rhoA, rhoB and rhoC genes wer e studied in human breast-cancer cell lines (HBCal), and in normal and immortalized mammary epithelial cells (HMEC) by Northern blot analysi s and in situ hybridization. In contrast to the ubiquitous rhoA and rh oC gene expression, dramatic variations in the mRNA level of the rhoB gene were evidenced. The rhoB mRNA level appeared to be inversely corr elated to the amounts of the epidermal-growth-factor(EGF) receptors in these cells. The rhoB transcripts were detected at high levels in ZR7 5-1, MCF7, HSL 53, HSL 59, HSL 90, T47D and SKBR3 HBCal, at hardly det ectable levels in BT 20, MDA-MB 231 and H466B HBCal and at intermediat e levels in normal and immortalized breast epithelial cells. Rapid and transient induction of the rhoB transcription was observed after EGF treatment in serum-deprived MDA-MB231, T47D and immortalized epithelia l cells. In contrast, no modulation of rhoB expression by EGF could be objectified in the MCF7 and ZR75-1 cell lines. Yet a normal function of EGF receptors was evidenced, since the immediate early gene c-fos w as rapidly induced, suggesting a constitutive expression of rhoB in th ese cell lines bypassing the regulation by EGF. In human mammary epith elial cells, rhoB mRNA is rapidly and transiently induced with EGF con centrations known to stimulate cell proliferation. This suggests that the rhoB product might be involved in a cascade that initiates or prom otes cell proliferation, and plays an important role in EGF-stimulated growth of breast normal and cancer cells. (C) 1994 Wiley-Liss, Inc.