کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2132173 | 1086677 | 2008 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Mutationally activated K-ras 4A and 4B both mediate lung carcinogenesis
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موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
To examine the roles of endogenous K-ras 4A and K-ras 4B splice variants in tumorigenesis, murine lung carcinogenesis was induced by N-methyl-N-nitrosourea (MNU), which causes a K-ras mutation (G12D) that jointly affects both isoforms. Compared with age-matched K-rastmÎ4A/â mice (where tumours can express mutationally activated K-ras 4B only), tumour number and size were significantly higher in K-ras+/â mice (where tumours can also express mutationally activated K-ras 4A), and significantly lower in K-rastmÎ4A/tmÎ4A mice (where tumours can express both wild-type and activated K-ras 4B). MNU induced significantly more, and larger, tumours in wild-type than K-rastmÎ4A/tmÎ4A mice which differ in that only tumours in wild-type mice can express wild-type and activated K-ras 4A. Lung tumours in all genotypes were predominantly papillary adenomas, and tumours from K-ras+/â and K-rastmÎ4A/â mice exhibited phospho-Erk1/2 and phospho-Akt staining. Hence (1) mutationally activated K-ras 4B is sufficient to activate the Raf/MEK/ERK(MAPK) and PI3-K/Akt pathways, and initiate lung tumorigenesis, (2) when expressed with activated K-ras 4B, mutationally activated K-ras 4A further promotes lung tumour formation and growth (both in the presence and absence of its wild-type isoform) but does not affect either tumour pathology or progression, and (3) wild-type K-ras 4B, either directly or indirectly, reduces tumour number and size.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Cell Research - Volume 314, Issue 5, 10 March 2008, Pages 1105-1114
Journal: Experimental Cell Research - Volume 314, Issue 5, 10 March 2008, Pages 1105-1114
نویسندگان
Charles E. Patek, Mark J. Arends, William A.H. Wallace, Feijun Luo, Suzanne Hagan, David G. Brownstein, Lorraine Rose, Paul S. Devenney, Marion Walker, Sarah J. Plowman, Rachel L. Berry, Walter Kolch, Owen J. Sansom, David J. Harrison, Martin L. Hooper,