BMP-induced growth suppression in colon cancer cells is mediated by p21WAF1 stabilization and modulated by RAS/ERK.

BMP-induced growth suppression in colon cancer cells is mediated by p21WAF1 stabilization and modulated by RAS/ERK. Research Abstract Details 

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BMP-induced growth suppression in colon cancer cells is mediated by p21WAF1 stabilization and modulated by RAS/ERK. Abstract Text:

Stayce E Beck,Barbara H Jung,Eunice Del Rosario,Jessica Gomez,John M Carethers,

Bone morphogenetic proteins (BMPs) regulate cell differentiation, proliferation, and apoptosis through a canonical SMAD signaling cascade. Absence of BMP signaling causes the formation of intestinal juvenile polyps in the colon cancer-prone syndrome familial juvenile polyposis. As sporadic colon cancers appear to have intact BMP signaling, we evaluated if K-RAS, driving a mitogenic pathway frequently activated in colon cancer, negatively affects BMP growth suppression. We treated non-tumorigenic but activated RAS/ERK FET cells with BMP2, and in combination with pharmacological or genetic inhibition of RAS/ERK, examined BMP-SMAD signaling, transcriptional activity, and cell growth, and also assessed p21(WAF1) mRNA, transcriptional activation, and protein levels. BMP2 increased nuclear phospho-SMAD1 2-fold, which increased another 2-3 fold when RAS/ERK was inhibited. BMP2 increased BMP-specific SMAD transcriptional activity 2-fold over control and decreased cell growth, but inhibition of RAS/ERK further enhanced BMP-specific transcriptional activity by an additional 1.5-2 fold and enhanced growth suppression by 20%. BMP-induced growth suppression is mediated in part by p21(WAF1), not by transcriptional upregulation but by improved p21 protein stability, which is inhibited by RAS/ERK. In colon cancer cells, BMP-SMAD signaling and growth suppression is facilitated by p21(WAF1) but modulated by oncogenic K-RAS to reduce the growth suppression directed by this pathway.

BMP-induced growth suppression in colon cancer cells is mediated by p21WAF1 stabilization and modulated by RAS/ERK. Publishing Authors By Initials

SE Beck,BH Jung,E Del Rosario,J Gomez,JM Carethers,

For similar enzymes and coenzymes: enzymes: hydrolases: acid anhydride hydrolases: gtp phosphohydrolases: gtp-binding proteins: monomeric gtp-binding proteins: ras proteins research abstracts see: enzymes and coenzymes: enzymes: hydrolases: acid anhydride hydrolases: gtp phosphohydrolases: gtp-binding proteins: monomeric gtp-binding proteins: ras proteins research

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BMP-induced growth suppression in colon cancer cells is mediated by p21WAF1 stabilization and modulated by RAS/ERK. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Cellular signalling

VOLUME: 19

Page Numbers: 1465-72

Journal Abbreviation: Cell. Signal.

ISSN: 0898-6568

DAY: 24

MONTH: 01

YEAR: 2007

BMP-induced growth suppression in colon cancer cells is mediated by p21WAF1 stabilization and modulated by RAS/ERK. Information

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LANGUAGE: eng

NlmUniqueID: 8904683

BMP-induced growth suppression in colon cancer cells is mediated by p21WAF1 stabilization and modulated by RAS/ERK. Keywords Mesh Terms:

KEYWORDS: ras Proteins

MESH TERMS: metabolism

Chemical & Substance for Abstract: BMP-induced growth suppression in colon cancer cells is mediated by p21WAF1 stabilization and modulated by RAS/ERK. Information

Substance Name: ras Proteins

Registry Number: EC 3.6.5.2

Grant and Affiliation Information for BMP-induced growth suppression in colon cancer cells is mediated by p21WAF1 stabilization and modulated by RAS/ERK.

AFFILIATION: Department of Medicine, Division of Gastroenterology, University of California-San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.

Country: England

AGENCY: United States NHLBI

GRANT: T32 HL 07212

ACRONYM: HL

MEDLINETA: Cell Signal

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