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The interferon‐inducible gene, Ifi204, acquires malignant transformation capability upon mutation at the Rb‐binding sites
Author(s) -
De Andrea Marco,
Ravotto Monica,
Noris Emanuela,
Ying Guo-Guang,
Gioia Daniela,
Azzimonti Barbara,
Gariglio Marisa,
Landolfo Santo
Publication year - 2002
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(02)02431-6
Subject(s) - transfection , microbiology and biotechnology , malignant transformation , mutant , mutation , cell culture , transformation (genetics) , retinoblastoma , biology , chemistry , cell , point mutation , gene , cancer research , genetics
p204 overexpression in retinoblastoma (Rb)−/− mouse embryo fibroblasts or transfection of p204 mutated at both Rb‐binding sites confer growth advantages, resulting in a significantly higher number of foci in a cell focus assay. To investigate the possibility that mutated p204 acquires malignant transformation capability, NIH3T3 cells were stably transfected with the expression vector pRcRSV204 double‐mutant (p204dm) harboring both the C‐terminal deletion up to amino acid 568 and the point mutation from glutamic acid to lysine at position 427, and analyzed for markers typical of cell immortalization and transformation. We detected a greater abundance of cell colonies in soft agar with p204dm‐expressing cells than vector control cells. The p204dm‐transfected cells also displayed two other characteristics associated with malignant transformation, i.e. growth under low‐serum conditions and formation of tumors in athymic nude mice. Moreover, their telomerase activity was significantly higher than in the vector control cells. It would thus seem that p204, devoid of functional Rb‐binding motifs, can become oncogenic.