Activated N-ras controls the transformed phenotype of HT1080 human fibrosarcoma cells

Enhanced expression of the urokinase-type plasminogen activator gene and reduced colony formation in soft agar by ectopic expression of PU.1 in HT1080 human fibrosarcoma cells

“…Similar observations have been reported in some tumours: constitutive expression of Ets-1 reverts the tumorigenicity in human colon cancer cells (Suzuki et al, 1996) and stable expression of a transdominant mutant of PU.1 or Ets-2 also reverts Ras-transformed NIH/3T3 cells (Langer et al, 1992;Wasylyk et al, 1994). It is known that HT1080 cells harbour the activated N-ras oncogene, which is essential for maintaining the transformed phenotypes of the cells, and inhibition of N-ras gene expression rendered the cells less malignant (Hall et al, 1983;Paterson et al, 1987). However, PU.1-transfected HT1080 cells expressed similar levels of N-ras mRNA to the parental cells and mock transfectants ( Figure 3A and B).…”

“…It has been reported that the activated N-ras gene is crucial for keeping the transformed phenotypes of HT1080 cells (Hall et al, 1983;Paterson et al, 1987) and that the elevated levels of expression of urokinase-type plasminogen activator (uPA) are associated with cell migration and malignant transformation in several types of tumour cells (Kirchheimer and Remold, 1989;Chambers et al, 1995). Therefore, we examined whether PU.…”

A novel styryl diphenylamine derivative reverts the transformed phenotype of human fibrosarcoma HT1080 cells

“…It is apparent that the slower growth rate in HT1080 cells treated with RX-465 could not be attributed to anomalous factors such as either acute or delayed cytotoxicity because the reproducibility in their growth rate was observed when the revertant cells were reioculated after achieving confluence. As a consequence of the simple reductions in mutant p2l1, as observed by Paterson et al (1987), similar morphological changes in HT1080 cells treated with RX-465 might indcate the possibility of a role for this compound in counteracting neoplastic transformation. Moreover, treatment of HT1080 cells with RX-465 resulted in a lower saturation density and inhibition of anchorage-independent growth in soft agar, both of which characteristics have been associated with reduction of tumour formation in mice, the most crifical phenotypic measure of cell transformation.…”

“…The revertant cells treated with RX-465 displayed a slower growth rate compared with cells treated with control vehicle, accompanied by morphological alterations of a flattened appearance which closely resembled revertants obtained by Paterson et al (1987) as selected from HT1080 cells by a suicide technique. It is apparent that the slower growth rate in HT1080 cells treated with RX-465 could not be attributed to anomalous factors such as either acute or delayed cytotoxicity because the reproducibility in their growth rate was observed when the revertant cells were reioculated after achieving confluence.…”

“…Finally, we found a novel and potent derivative, RX465, dissimilar to conventional anti-cancer drugs in chemical strucre. We predicted that the styryl diphenylamine derivative would be able to reduce the malignant phenotype of tumour ells, because the cell morphology induced by this compound is closely related to that of the flat revertant, showing reduction of mutant N-ras gene product p21 (p21IN), which par-ticipates in the control of this transformed phenotype as shown in HT1080 cells using a suicide technique (Paterson et al, 1987).…”