NDLI: Loss of RhoA Exacerbates, Rather Than Dampens, Oncogenic K-Ras Induced Lung Adenoma Formation in Mice

Content Provider	PubMed Central
Author	Zandvakili, Inuk Davis, Ashley Kuenzi Hu, Guodong Zheng, Yi
Editor	Hansen, Steen Henning
Copyright Year	2015
Abstract	Numerous cellular studies have indicated that RhoA signaling is required for oncogenic Ras-induced transformation, suggesting that RhoA is a useful target in Ras induced neoplasia. However, to date very limited data exist to genetically attribute RhoA function to Ras-mediated tumorigenesis in mammalian models. In order to assess whether RhoA is required for K-Ras-induced lung cancer initiation, we utilized the K-RasG12D Lox-Stop-Lox murine lung cancer model in combination with a conditional RhoAflox/flox and RhoC-/- knockout mouse models. Deletion of the floxed Rhoa gene and expression of K-RasG12D was achieved by either CCSP-Cre or adenoviral Cre, resulting in simultaneous expression of K-RasG12D and deletion of RhoA from the murine lung. We found that deletion of RhoA, RhoC or both did not adversely affect normal lung development. Moreover, we found that deletion of either RhoA or RhoC alone did not suppress K-RasG12D induced lung adenoma initiation. Rather, deletion of RhoA alone exacerbated lung adenoma formation, whereas dual deletion of RhoA and RhoC together significantly reduced K-RasG12D induced adenoma formation. Deletion of RhoA appears to induce a compensatory mechanism that exacerbates adenoma formation. The compensatory mechanism is at least partly mediated by RhoC. This study suggests that targeting of RhoA alone may allow for compensation and a paradoxical exacerbation of neoplasia, while simultaneous targeting of both RhoA and RhoC is likely to lead to more favorable outcomes.
Related Links	http://dx.doi.org/10.1371/journal.pone.0127923
Starting Page	127923
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	6
Volume Number	10
Language	English
Publisher	Public Library of Science
Publisher Date	2015-06-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Spred-2 Deficiency Exacerbates Lipopolysaccharide-Induced Acute Lung Inflammation in Mice

Rhinovirus Exacerbates House-Dust-Mite Induced Lung Disease in Adult Mice

Hyperglycemia Promotes K-Ras-Induced Lung Tumorigenesis through BASCs Amplification

Cooperativity of Oncogenic K-Ras and Downregulated p16/INK4A in Human Pancreatic Tumorigenesis

Stiffness-Activated GEF-H1 Expression Exacerbates LPS-Induced Lung Inflammation

Nicotinamide Exacerbates Hypoxemia in Ventilator-Induced Lung Injury Independent of Neutrophil Infiltration

Autophagy in oncogenic K-Ras promotes basal extrusion of epithelial cells by degrading S1P

Correction: Nicotinamide Exacerbates Hypoxemia in Ventilator-Induced Lung Injury Independent of Neutrophil Infiltration

Oncogenic K-Ras and Loss of Smad4 Mediate Invasion by Activating an EGFR/NF-κB Axis That Induces Expression of MMP9 and uPA in Human Pancreas Progenitor Cells

Loss of RhoA Exacerbates, Rather Than Dampens, Oncogenic K-Ras Induced Lung Adenoma Formation in Mice

Similar Documents

Spred-2 Deficiency Exacerbates Lipopolysaccharide-Induced Acute Lung Inflammation in Mice

Rhinovirus Exacerbates House-Dust-Mite Induced Lung Disease in Adult Mice

Hyperglycemia Promotes K-Ras-Induced Lung Tumorigenesis through BASCs Amplification

Cooperativity of Oncogenic K-Ras and Downregulated p16/INK4A in Human Pancreatic Tumorigenesis

Stiffness-Activated GEF-H1 Expression Exacerbates LPS-Induced Lung Inflammation

Nicotinamide Exacerbates Hypoxemia in Ventilator-Induced Lung Injury Independent of Neutrophil Infiltration

Autophagy in oncogenic K-Ras promotes basal extrusion of epithelial cells by degrading S1P

Correction: Nicotinamide Exacerbates Hypoxemia in Ventilator-Induced Lung Injury Independent of Neutrophil Infiltration

Oncogenic K-Ras and Loss of Smad4 Mediate Invasion by Activating an EGFR/NF-κB Axis That Induces Expression of MMP9 and uPA in Human Pancreas Progenitor Cells

Loss of RhoA Exacerbates, Rather Than Dampens, Oncogenic K-Ras Induced Lung Adenoma Formation in Mice