Thursday, August 21, 2025 8/21/2025

Regulation of cyclin D1 expression in the intestine

Award Number: R01DK060632
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/15/2002
PERIOD OF PERFORMANCE END DATE: 11/30/2014

Group Awards By:

View Award Description

Regulation of cyclin D1 expression in the intestine - DESCRIPTION (from the applicant): Cyclin D1 is a tightly regulated cell cycle control molecule that functions as a critical sensor of extracellular growth stimulatory and inhibitory signals and a key determinant of progression through G1 phase. Aberrant expression of cyclin D1 is one of the most frequent abnormalities in human cancer, and is believed to play an important role in tumorigenesis. Understanding of the mechanisms underlying control of cyclin D1 accumulation under normal and pathological conditions is, therefore, of key importance. Our studies have identified protein kinase C a (PKCa) as a novel regulator of cyclin D1 expression in intestinal epithelial cells. PKCa exhibits growth inhibitory and tumor suppressor properties in the intestine, and its expression is lost early during intestinal tumor development. Based on extensive new data, strategies are proposed to address the hypothesis that PKCa signaling plays a critical role in regulating the expression of cyclin D1 in intestinal cells, and that disruption of PKCa-mediated cyclin D1 control contributes to intestinal neoplasia. The following key findings provide the foundation for this hypothesis: (a) PKCa activity represses cyclin D1 accumulation in non-transformed intestinal cells by two mechanisms: inhibition of cap-dependent translation initiation and blockade of cyclin D1 mRNA accumulation; (b) inhibitory effects of PKCa on cyclin D1 translation involve activation of the translational repressor 4E-BP1; (c) loss of PKCa signaling is associated with hyperinduction of cyclin D1 mRNA and protein and increased cell proliferation, and (c) restoration of PKCa in colon cancer cells represses cyclin D1 mRNA and protein and inhibits anchorage-independent growth. To explore further the link between PKCa signaling and control of cyclin D1 accumulation in intestinal cells, the following Specific Aims will be addressed: (1) To determine the mechanisms by which PKCa signaling modulates PP2A activity and 4E-BP1 hypophosphorylation/activation to effect cyclin D1 loss in intestinal cells, (2) To explore the role of Id1 suppression in PKCa-induced downregulation of cyclin D1 in normal and neoplastic intestinal cells, (3) To investigate the mechanisms involved in cyclin D1 mRNA hyperinduction associated with loss of PKCa signaling in intestinal epithelial cells, and (4) To explore the role of PKCa signaling in regulation of cyclin D1 levels and maintenance of intestinal homeostasis in vivo. The long-term goals of this project are to understand the mechanisms that orchestrate the process of intestinal epithelial renewal under normal conditions, to determine how intestinal cells overcome these controls to produce tumors, and to identify novel targets for prevention and therapy of intestinal cancer. PUBLIC HEALTH RELEVANCE: Cyclin D1 plays a critical role in regulation of cell growth and survival. Although increased expression of this molecule is one of the most common abnormalities in human cancer, the mechanisms underlying its aberrant accumulation are poorly understood. We have identified PKCa, which is lost early during intestinal tumorigenesis, as a novel repressor of cyclin D1 levels in intestinal cells. Understanding of the interplay between PKCa and cyclin D1 may identify new leads for prevention and/or therapy of intestinal tumors.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2018 ( Subtotal = $0 )
2018	2014	UNIVERSITY OF NEBRASKA	987835 NEBRASKA MEDICAL CENTER	OMAHA	NE	68198	DOUGLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	11	3/30/2018	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2017 ( Subtotal = $0 )
2017	2014	UNIVERSITY OF NEBRASKA	987835 NEBRASKA MEDICAL CENTER	OMAHA	NE	68198	DOUGLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	11	11/30/2016	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2016 ( Subtotal = $0 )
2016	2014	UNIVERSITY OF NEBRASKA MEDICAL CENTER	987835 NEBRASKA MEDICAL CENTER	OMAHA	NE	68198	DOUGLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	11	11/30/2015	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2014 ( Subtotal = $145,125 )
2014	2014	UNIVERSITY OF NEBRASKA MEDICAL CENTER	987835 NEBRASKA MEDICAL CENTER	OMAHA	NE	68198	DOUGLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	11	2/21/2014	NON-COMPETING CONTINUATION	$1,998
2014	2014	UNIVERSITY OF NEBRASKA MEDICAL CENTER	987835 NEBRASKA MEDICAL CENTER	OMAHA	NE	68198	DOUGLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	11	11/22/2013	NON-COMPETING CONTINUATION	$17,977
2014	2014	UNIVERSITY OF NEBRASKA MEDICAL CENTER	987835 NEBRASKA MEDICAL CENTER	OMAHA	NE	68198	DOUGLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	11	7/11/2014	SUPPLEMENT FOR EXPANSION	$125,150
														Subtotal = $145,125

Issue Date FY: 2013 ( Subtotal = $251,706 )
2013	2013	UNIVERSITY OF NEBRASKA MEDICAL CENTER	987835 NEBRASKA MEDICAL CENTER	OMAHA	NE	68198	DOUGLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	10	5/17/2013	NON-COMPETING CONTINUATION	$19,129
2013	2013	UNIVERSITY OF NEBRASKA MEDICAL CENTER	987835 NEBRASKA MEDICAL CENTER	OMAHA	NE	68198	DOUGLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	10	11/30/2012	NON-COMPETING CONTINUATION	$232,577
														Subtotal = $251,706

Issue Date FY: 2012 ( Subtotal = $293,987 )
2012	2012	UNIVERSITY OF NEBRASKA MEDICAL CENTER	987835 NEBRASKA MEDICAL CENTER	OMAHA	NE	68198	DOUGLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	003	9	3/23/2012	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$293,987
2012	2012	HEALTH RESEARCH, INC - ROSWELL PARK DIVISION	666 ELM STREET	BUFFALO	NY	14203	ERIE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	8	3/22/2012	NON-COMPETING CONTINUATION	-$326,278
2012	2012	HEALTH RESEARCH, INC - ROSWELL PARK DIVISION	666 ELM STREET	BUFFALO	NY	14203	ERIE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	8	11/17/2011	NON-COMPETING CONTINUATION	$293,650
2012	2012	HEALTH RESEARCH, INC - ROSWELL PARK DIVISION	666 ELM STREET	BUFFALO	NY	14203	ERIE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	8	2/1/2012	NON-COMPETING CONTINUATION	$32,628
														Subtotal = $293,987

Issue Date FY: 2011 ( Subtotal = $322,343 )
2011	2011	HEALTH RESEARCH, INC - ROSWELL PARK DIVISION	666 ELM STREET	BUFFALO	NY	14203	ERIE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	7	5/24/2011	NON-COMPETING CONTINUATION	$29,303
2011	2011	HEALTH RESEARCH, INC - ROSWELL PARK DIVISION	666 ELM STREET	BUFFALO	NY	14203	ERIE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	7	2/24/2011	NON-COMPETING CONTINUATION	$293,040
														Subtotal = $322,343

Issue Date FY: 2010 ( Subtotal = $0 )
2010	2009	HEALTH RESEARCH, INC - ROSWELL PARK DIVISION	666 ELM STREET	BUFFALO	NY	14203	ERIE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	6	1/28/2010	COMPETING CONTINUATION	-$321,744
2010	2009	HEALTH RESEARCH, INC - ROSWELL PARK DIVISION	666 ELM STREET	BUFFALO	NY	14203	ERIE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	6	2/2/2010	COMPETING CONTINUATION	$321,744
														Subtotal = $0

Issue Date FY: 2009 ( Subtotal = $321,744 )
2009	2009	HEALTH RESEARCH, INC - ALBANY DIVISION	1 UNIVERSITY PLACE	RENSSELAER	NY	12144	RENSSELAER	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	6	9/28/2009	COMPETING CONTINUATION	$321,744
														Subtotal = $321,744

Issue Date FY: 2006 ( Subtotal = $260,447 )
2006	2006	NY ST DEPARTMENT OF HEALTH & HEALTH RESEARCH, INC	666 ELM STREET	BUFFALO	NY	14263	ERIE	USA	Digestive Diseases and Nutrition Research	000	5	1/30/2006	NON-COMPETING CONTINUATION	$260,447
														Subtotal = $260,447

Issue Date FY: 2005 ( Subtotal = $263,315 )
2005	2005	NY ST DEPARTMENT OF HEALTH & HEALTH RESEARCH, INC	666 ELM STREET	BUFFALO	NY	14263	ERIE	USA	Digestive Diseases and Nutrition Research	000	4	1/12/2005	NON-COMPETING CONTINUATION	$263,315
														Subtotal = $263,315

Issue Date FY: 2004 ( Subtotal = $260,015 )
2004	2004	NY ST DEPARTMENT OF HEALTH & HEALTH RESEARCH, INC	666 ELM STREET	BUFFALO	NY	14263	ERIE	USA	Digestive Diseases and Nutrition Research	000	3	2/3/2004	NON-COMPETING CONTINUATION	$260,015
														Subtotal = $260,015

Issue Date FY: 2003 ( Subtotal = $256,811 )
2003	2003	NY ST DEPARTMENT OF HEALTH & HEALTH RESEARCH, INC	666 ELM STREET	BUFFALO	NY	14263	ERIE	USA	Digestive Diseases and Nutrition Research	000	2		NON-COMPETING CONTINUATION	$256,811
														Subtotal = $256,811

Issue Date FY: 2002 ( Subtotal = $253,699 )
2002	2002	NY ST DEPARTMENT OF HEALTH & HEALTH RESEARCH, INC	666 ELM STREET	BUFFALO	NY	14263	ERIE	USA	Digestive Diseases and Nutrition Research	000	1	2/7/2002	NEW	$253,699
														Subtotal = $253,699

Grand Total All Awards = $2,629,192

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Regulation of cyclin D1 expression in the intestine

Award Number: R01DK060632

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 02/15/2002

PERIOD OF PERFORMANCE END DATE: 11/30/2014

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer