ABSTRACT
The concept has now gained wide acceptance that carcinogenesis is a multistep process. After the two operationally defined stages termed “initiation” and “promotion”, more steps seem required before full-fledged malignancy arises, corresponding to transplantable tumors. The complexity of the functions needed to express complete malignancy makes it unlikely that a single oncogene or even two oncogenes, or a successive series of random, stable changes would be sufficient for explaining cancer. Accordingly, gap-junction-mediated intercellular communication between hepatocytes is transiently inhibited by the tumor promoter phénobarbital,65 and maintenance of cell-to-cell communication indeed correlated with the sensitivity of oncogene-transformed cells to the suppressive influence of normal density-arrested cells. Extension of the concept of cancer suppressor genes rests on early experiments showing that hybridization between normal and transformed cells might suppress the malignant phenotype.
