Uncovering novel targets for cancer chemoprevention.

Uncovering novel targets for cancer chemoprevention. Research Abstract Details 

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Uncovering novel targets for cancer chemoprevention. Abstract Text:

Konstantin H Dragnev,Qing Feng,Yan Ma,Sumit J Shah,Candice Black,Vincent Memoli,William Nugent,James R Rigas,Sutisak Kitareewan,Sarah Freemantle,Ethan Dmitrovsky,

Tobacco carcinogen treatment of immortalized human bronchial epithelial (HBE) cells has uncovered novel targets for cancer chemoprevention. Experiments were conducted with HBE cells and independent treatments with tobacco carcinogens along with the chemopreventive agent all-trans-retinoic acid (RA). That work highlighted D-type and E-type cyclins as novel molecular pharmacologic targets of several chemopreventive agents. G1 cyclins are often aberrantly expressed in bronchial preneoplasia and lung cancers. This implicated these species as targets for clinical cancer chemoprevention. Retinoid regulation mechanisms of D-type cyclins in lung cancer chemoprevention have been comprehensively explored. Retinoid chemoprevention has been mechanistically linked to proteasomal degradation of cyclin D1 and cyclin D3. Threonine 286 mutation stabilized cyclin D1, implicating phosphorylation in this retinoid chemoprevention. Studies with a phospho-specific anti-cyclin D1 antibody confirmed this hypothesis. Glycogen synthase kinase (GSK) inhibitors established a role for this kinase in the retinoid regulation of cyclin D1, but not cyclin D3. Involvement of D-type cyclins in this chemoprevention was shown using small interfering RNAs (siRNAs). Gene profiling experiments highlighted the E1-like ubiquitin-activating enzyme (UBE1L) in the retinoid regulation of cyclin D1. Proof of principle trials have translated these studies into the clinic and established that chemopreventive agents can target D-type cyclins. These findings have been built upon with a targeted combination regimen that cooperatively affects D-type cyclins. Taken together, these preclinical and clinical findings strongly implicate these cyclins as novel molecular pharmacological targets for cancer chemoprevention.

Uncovering novel targets for cancer chemoprevention. Publishing Authors By Initials

KH Dragnev,Q Feng,Y Ma,SJ Shah,C Black,V Memoli,W Nugent,JR Rigas,S Kitareewan,S Freemantle,E Dmitrovsky,

For similar neoplasms research abstracts see: neoplasms research

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Uncovering novel targets for cancer chemoprevention. Journal Published:

PUBLICATION TYPE: Review

Journal: Recent results in cancer research. Fortschritte de

VOLUME: 174

Page Numbers: 235-43

Journal Abbreviation: Recent Results Cancer Res.

ISSN: 0080-0015

DAY: 13

MONTH: 02

YEAR: 2007

Uncovering novel targets for cancer chemoprevention. Information

Number of References: 42

LANGUAGE: eng

NlmUniqueID: 44671

Uncovering novel targets for cancer chemoprevention. Keywords Mesh Terms:

KEYWORDS: Neoplasms

MESH TERMS: prevention & control

Chemical & Substance for Abstract: Uncovering novel targets for cancer chemoprevention. Information

Substance Name: Cyclin D1

Registry Number: 136601-57-5

Grant and Affiliation Information for Uncovering novel targets for cancer chemoprevention.

AFFILIATION: Department of Medicine, Dartmouth Medical School, Hanover, NH 03755, USA.

Country: Germany

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MEDLINETA: Recent Results Cancer Res

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