Expression of H-ras correlates with metastatic potential: evidence for direct regulation of the metastatic phenotype in 10T1/2 and NIH 3T3 cells.
Using three independent approaches, we studied the effects of H-ras on metastasis formation. Analysis of five in vitro-ras-transfected 10T1/2 clones with either flat or refractile morphologies revealed a relationship between metastatic potential, H-ras expression, and anchorage-independent growth. Four metastatic variants derived from a poorly metastatic, low-H-ras-expressing line all expressed high levels of H-ras RNA and grew efficiently in soft agar. Activation of H-ras expression in the metastatic tumors had occurred through amplification and rearrangement of H-ras sequences. In addition, preinduction of p21 synthesis in NIH 3T3 line 433, which contains v-H-ras under transcriptional control of the glucocorticoid-sensitive mouse mammary tumor virus long terminal repeat, significantly increased metastatic efficiency. Glucocorticoid treatment of normal or pEJ-transformed NIH 3T3 cells did not affect metastatic potential. These data reveal a direct relationship between ras expression and metastasis formation and suggest that metastatic and transformed phenotypes may be coregulated in ras-transformed 10T1/2 and NIH 3T3 cells.
D000818:Animals; D002460:Cell Line; D019204:GTP-Binding Proteins / Q000235:genetics; D005786:Gene Expression Regulation; D051379:Mice; D008815:Mice, Inbred Strains; D009362:Neoplasm Metastasis; D009374:Neoplasms, Experimental / Q000235:genetics / Q000473:pathology*; D009857:Oncogenes; D012333:RNA, Messenger / Q000235:genetics
D012333:RNA, Messenger; D019204:GTP-Binding Proteins