Loss of c-abl facilitates anchorage-independent growth of p53- and RB- deficient primary mouse embryonic fibroblasts.
The c-abl tyrosine kinase is the proto-oncogene of the v-abl oncogene of the Abelson murine leukemia virus. Although mutational variants of c-Abl can exhibit gain of function and can produce a transformed phenotype, the function of c-Abl in transformation remained unclear. Here, we report that the loss of c-abl facilitates transformation. c-abl-knockout mouse embryonic fibroblasts (MEFs) immortalized by SV40 T antigen acquired anchorage-independent growth, and by constructing mutational variants of T antigen we showed that binding of large T antigen to p53 and RB was necessary to induce anchorage-independent growth. Although c-abl/p53 double-knockout MEFs did not undergo anchorage-independent growth, those expressing human papilloma virus 16 E7, which mainly inactivates RB, did. Our results show that the loss of c-abl facilitates anchorage-independent growth in the context of p53 and RB deficiency, and suggest that loss of function of c-abl facilitates some types of transformation.
Suzuki
Jun
J
Laboratory of Molecular Oncology, Osaka Bioscience Institute, 6-2-4 Furuedai, Suita, Osaka 565-0874, Japan.
Sukezane
Taiko
T
Akagi
Tsuyoshi
T
Georgescu
Maria Magdalena
MM
Ohtani
Mayumi
M
Inoue
Hirokazu
H
Jat
Parmjit S
PS
Goff
Stephen P
SP
Hanafusa
Hidesaburo
H
Shishido
Tomoyuki
T
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism; D051379:Mice; D009856:Oncogene Proteins, Viral / Q000378:metabolism; D050725:Papillomavirus E7 Proteins; D000090063:Proto-Oncogene Mas; D016315:Proto-Oncogene Proteins c-abl / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000172:deficiency*; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency*
D000952:Antigens, Polyomavirus Transforming; C000715470:MAS1 protein, human; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D000090063:Proto-Oncogene Mas; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; C059731:oncogene protein E7, Human papillomavirus type 16; D016315:Proto-Oncogene Proteins c-abl