Association of viral oncogene-induced changes in gap junctional intercellular communication and morphological transformation in BALB/c3T3 cells.
In order to study the relationship between altered gap junctional intercellular communication (GJIC) and induction of cell transformation by oncogenes, we transfected six viral oncogenes into BALB/c3T3 A31-1-1 cells. BALB/c3T3 cells with v-src, v-ras or polyoma middle T (PyMT) genes grew in soft agar and formed distinct transformed foci in the absence or presence of a vast excess of non-transfected cells. On the other hand, those with v-myc, v-fos or polyoma large T (PyLT) genes expressed less distinctly transformed phenotypes (less transformed morphology, higher saturation density than non-transfected counterparts and less growth in soft agar), and did not form distinct foci in coculture with non-transformed cells. When their homologous GJIC capacities were examined by the microinjection/dye transfer assay, no decrease in GJIC was observed in any of the v-onc-transformed cells. Non-transformed and all v-onc-transformed cell lines expressed similar levels of connexin 43 mRNA. v-myc-, v-fos- and PyLT-transformed cells, but not v-ras-, v-src- and PyMT-transformed cells were able to communicate heterologously with non-transformed cells. Tumor promoting phorbol esters strongly inhibited GJIC of non-transformed and all v-onc-transformed BALB/c3T3 cell lines. In cocultures of v-myc-, v-fos- or PyLT-transformed cells with non-transformed BALB/c3T3 A31-1-1 cells, 12-O-tetradecanoylphorbol-13-acetate (TPA) increased the number of transformed foci. However, when these v-onc-transformed cells were co-cultured with non-transformed BALB/c3T3 A31-1-13 cells (which lose GJIC at growth confluence, as if TPA had been added), no morphologically transformed foci appeared. These results suggest that factors other than GJIC are involved in the suppression of oncogene-transformed cells by surrounding normal counterparts.
Unit of Multistage Carcinogenesis, International Agency for Research on Cancer, Lyon, France.
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F
Katoh
J L
JL
Klein
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Bignami
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H
Yamasaki
D016475:3T3 Cells; D000818:Animals; D002450:Cell Communication; D002471:Cell Transformation, Neoplastic; D017630:Connexins; D005814:Genes, Viral; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D009857:Oncogenes; D014162:Transfection
D017630:Connexins; D008565:Membrane Proteins