Carcinogenesis, Vol 19, 463-470, Copyright © 1998 by Oxford University Press
G Ramakrishna and LM Anderson
Mutational activation of the K-ras oncogene often occurs in human and mouse
lung adenocarcinomas. Since K-ras p21 functions in trans-membrane
signaling, we have investigated whether the amount of this protein in lung
cell membranes is a variable that could influence lung tumorigenesis,
either due to genetic differences or in response to tumor promoters. The
six mouse strains assessed showed little difference in the total lung K-ras
p21 after immunoprecipitation and immunoblotting. However, amount of ras
p21 in the membrane fraction showed significant differences, with C57BL/6
and BALB/c having 3-5-fold more than NIH Swiss, AKR and DBA mice.
Interestingly, a congenic AKR strain having the Ahr(b-1) Ah receptor allele
from C57BL/6 mice (designated AKR.B6Ah) had high lung membrane K-ras p21
similar to that of C57BL/6. To test for possible changes related to lung
tumor promotion, mice were treated with a promotional dose of TCDD (5
nmol/kg). After 48 h C57BL/6 lungs showed an increase in p21 in both total
and membrane fractions. BALB/c, DBA and Swiss mice showed an increase only
in membranes. There was no change in the AKR and AKR.B6Ah. Aroclor 1254
(250 mg/kg) caused an increase in membrane/cytosol ratio in Swiss mice.
Thus the membrane:cytosol K-ras p21 ratio may be influenced by the Ahr
phenotype, and TCDD and PCBs can induce p21 or increase its membrane level
in certain strains, but these properties are not fully dependent on Ahr
receptor type. In confirmation of the relevance of these findings for the
tumor target cell type, the immortalized alveolar type 2 E10 cell line
presented K- ras p21 in membrane, and this was increased 4-fold by
treatment with 10 nM TCDD.
ARTICLES
Levels and membrane localization of the c-K-ras p21 protein in lungs of mice of different genetic strains and effects of 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD) and Aroclor 1254
Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702, USA.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. Alguacil, M. Porta, N. Malats, T. Kauppinen, M. Kogevinas, F. G. Benavides, T. Partanen, and A. Carrato Occupational exposure to organic solvents and K-ras mutations in exocrine pancreatic cancer Carcinogenesis, January 1, 2002; 23(1): 101 - 106. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. A. Diwan, G. Ramakrishna, L. M. Anderson, and D. Ramljak Overexpression of Grb2 in Inflammatory Lesions and Preneoplastic Foci and Tumors Induced by N-Nitrosodimethylamine in Helicobacter hepaticus--Infected and -Noninfected A/J Mice Toxicol Pathol, July 1, 2000; 28(4): 548 - 554. [Abstract] [PDF]
|
|