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Publication : Increased K-ras protein and activity in mouse and human lung epithelial cells at confluence.

First Author  Kammouni W Year  2002
Journal  Cell Growth Differ Volume  13
Issue  9 Pages  441-8
PubMed ID  12354753 Mgi Jnum  J:327412
Mgi Id  MGI:7332755 Citation  Kammouni W, et al. (2002) Increased K-ras protein and activity in mouse and human lung epithelial cells at confluence. Cell Growth Differ 13(9):441-8
abstractText  Although K-ras is frequently mutated in lung adenocarcinomas, the normal function of K-ras p21 in lung is not known. In two mouse (E10 and C10) and one human (HPL1D) immortalized lung cell lines from peripheral epithelium, we have measured total K-ras p21 and active K-ras p21-GTP during cell proliferation and at growth arrest caused by confluence. In all three cell types, total K-ras p21 increased 2- to 4-fold at confluence, and active K-ras p21-GTP increased 10- to 200-fold. It was estimated that 0.03% of total K-ras p21 was in the active GTP-bound state at 50% confluence, compared with 1.4% at postconfluence. By contrast, stimulation of proliferation by serum-containing medium did not involve K-ras p21 activation, even though a rapid, marked activation of both Erk1/2 and Akt occurred. At confluence, large increases, up to 14-fold, were seen in Grb2/Sos1 complexes, which may activate K-ras p21. In sum, increased protein expression and activity of K-ras p21 are associated with growth arrest, not with proliferation, in mouse and human lung cell lines.
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