A genetic model for undifferentiated cell tumor formation: similar tumors formed by different cell lines transformed by the E1A oncogene.
The activation of oncogenes and the mutation/deletion of suppressor genes may be involved in tumor heterogeneity. In an attempt to study tumor heterogeneity, we transformed cell lines from epithelial (PAM 212), mesenchymal (NIH-3T3), or melanocytic origin (L-BIOBR) with the wild type E1a oncogene. To make the cell lines tumorigenic, cells were infected with Harvey sarcoma virus carrying the v-H-ras oncogene. The transformed cells were injected into nude mice and the tumors studied by optical and electron microscopy. The tumors formed by v-H-ras-transformed cells consisted of epitheliod melanomas, spindle cells sarcomas and poorly-differentiated carcinomas, depending on the cell of origin. In contrast, the tumors obtained from cells also carrying the E1a oncogene showed a predominant small and undifferentiated cell pattern regardless of the cell of origin. We conclude that the E1a oncogene products induce a negative control of differentiation, independent of the cell type, and that tumors formed by cells carrying the E1a oncogene display an undifferentiated cell pattern.
Ramón y Cajal
S
S
Department of Pathology, Clinica Puerta de Hierro, Madrid, Spain.
Sánchez-Prieto
R
R
Anaya
A
A
D017500:Adenovirus E1A Proteins / Q000235:genetics*; D000818:Animals; D015153:Blotting, Western; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology*; D011905:Genes, ras / Q000235:genetics; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D008854:Microscopy, Electron; D009857:Oncogenes / Q000235:genetics*; D014407:Tumor Cells, Cultured
D017500:Adenovirus E1A Proteins