Table 1.
Activity of Met mutants
Met construct* | Met phos-phorylation† | Focus formation‡ #foci/μg DNA | Tumor formation§
|
|
---|---|---|---|---|
# mice with tumors/# mice injected | Mean tumor size, mm2 | |||
Wild type | − | 0 | 0/14¶ | 0¶ |
M1268T(s) | +++ | >300 | 8/8 | 216 ± 77 |
Y1248H(s) | ++ | 156 ± 16 | 8/8 | 100 ± 40 |
D1246H(s) | ++ | 119 ± 16 | 8/8 | 60 ± 52 |
D1246N(g) | ++ | 147 ± 5 | 9/9 | 50 ± 25 |
Y1248C(g) | ++ | 115 ± 11 | 7/8 | 77 ± 89 |
V1238l(g) | ++ | 0 | 5/8 | 13 ± 15 |
V1206L(g) | + | 0 | 6/6 | 50 ± 32 |
M1149T(g) | + | 0 | 4/8 | 46 ± 56 |
See legend to Fig. 1.
Data from Fig. 1A (and data not shown).
NIH 3T3 cells transfected with the indicated constructs were scored for focus formation after 2 weeks. Results represent the mean of two independent experiments. Also see Fig. 2.
NIH 3T3 cells transfected with the indicated constructs were inoculated subcutaneously into nude mice, and tumors were measured after 2 weeks. Results represent the mean of two independent experiments.
Cells transfected with wild-type Met do eventually form tumors, probably due to the generation of an autocrine Met-HGF/SF stimulatory loop, as we previously described (29). However, tumors derived from cells expressing wild-type Met do not appear until ∼4 weeks after inoculation, by which time most mice inoculated with cells expressing mutant Met molecules have had to be sacrificed due to tumor burden.