| First Author | Nakagama H | Year | 1997 |
| Journal | Proc Natl Acad Sci U S A | Volume | 94 |
| Issue | 20 | Pages | 10813-6 |
| PubMed ID | 9380716 | Mgi Jnum | J:43490 |
| Mgi Id | MGI:1097794 | Doi | 10.1073/pnas.94.20.10813 |
| Citation | Nakagama H, et al. (1997) Induction of minisatellite mutation in NIH 3T3 cells by treatment with the tumor promoter okadaic acid. Proc Natl Acad Sci U S A 94(20):10813-6 |
| abstractText | Okadaic acid (OA) is a strong tumor promoter of mouse skin carcinogenesis and also a potent inhibitor of serine/threonine protein phosphatases. OA induces various genetic alterations in cultured cells, such as diphtheria-toxin-resistance mutations, sister chromatid exchange, exclusion of exogenous transforming oncogenes, and gene amplification. The present study revealed that it caused minisatellite mutation (MSM) at a high frequency in NIH 3T3 cells, although no microsatellite mutation was found. Nine of 31 clones (29%) exhibited MSM after 6 days of OA treatment, as opposed to only 1 of 30 clones (3%) without OA exposure. Moreover, NIH 3T3 cells treated with OA acquired tumorigenicity in nude mice, giving rise to 7 tumors within 25 weeks in 20 sites where 3 x 10(6) cells were injected. In contrast, the same numbers of untreated cells gave rise to only one tumor, and the tumor grew much slower. All of three OA-induced tumors examined manifested the MSM. The findings thus point to a molecular mechanism by which OA could function as a tumor promoter, and also the biological relevance of the induction of MSM in the tumorigenic process by OA. |
