Neoplastic transformation of rat 3Y1 cells by a transcriptionally activated human c-myc gene and stabilization of p53 cellular tumor antigen in the transformed cells.

Abstract

Transformed foci were obtained in rat 3Y1 fibroblasts cotransfected wtih pRmyc 27 (transcriptionally activated c-myc) and pSV2neo DNA. RmycY cell lines (1 to 7) were established from these foci. RmycY cells were small and round and contained enlarged nucleoli in the nucleus. The myc gene was expressed in these cell lines at a much higher level than in 3Y1 cells and at a level similar to that in HL-60 cells. These cell lines formed colonies in soft-agar culture and tumors in syngeneic rats transplanted with RmycY cells. Expression of the gene and colony formation in soft-agar culture were analyzed in subclones from RmycY cell line 1. A correlation between myc gene expression and the ability to form colonies in soft-agar culture was observed in these cells. Antibody against p53 cellular tumor antigen was detected in some sera from tumor-bearing rats. p53 cellular tumor antigen stabilized and accumulated in RmycY cells to the same extent as in simian virus 40-transformed cells. The results suggest that elevated c-myc expression and an increased amount of p53 cause 3Y1 cells to become a more tumorigenic cell line.

Cloning of mid-G1 serum response genes and identification of a subset regulated by conditional myc expression.

“…This identifies p53 as a target, direct or indirect, of myc in this system. This result is consistent with previous observations that p53 is among the proteins that are overexpressed in cells whose growth characteristics have been altered by chronic c-myc overexpression (Shiroki et al, 1986), although it has been difficult in such systems to discriminate obligate responses to myc from long term indirect effects. As discussed later, other independent molecular data argue that p53 is a good candidate for direct regulation by myc.…”

p53 gene mutations and protein accumulation in human ovarian cancer.

“…Since increased levels of mutated p53 protein may be necessary for inactivation of wild-type p53 protein (29)(30)(31), the biological consequences of different mutations may vary. Even among mutations leading to accumulation of p53 protein, there is variable malignant potential (2,7,28).…”

Altered protein glycosylation of rat 3Y1 cells induced by activated c‐myc gene

“…In this study, we have comparatively analyzed the N-linked sugar-chain structures of cell-membrane giycoproteins ob-tained from rat 3Yl cells and their c-myc-transfected cells which express the c-myc gene at a 20 to 40 times higher level than control 3Y 1 cells and exhibit high tumorigenicity when injected into syngeneic newborn rats (Shiroki et al, 1986). The results indicated that tri-and tetra-antennary oligosaccharides having the GlcNAcP 1-+6 branching and/or the GlcNAcP 1+4 branching increase with the decrease of biantennary oligosaccharides in the transfected cells.…”

“…RmycY 1 cells thus established as a transformed cell line expressed the c-myc gene at a much higher level than 3Y 1 cells and formed colonies in soft-agar culture and tumors in syngeneic rats (Shiroki et al, 1986). Cells were cultured as described previously (Shiroki et al, 1986) and harvested at logarithmic phase by scraping into phosphate-buffered saline, PH 7.4. The harvested cells were disrupted in hypotonic solution and subjected to the centrifugation procedure to obtain the membrane preparation as described previously .…”