| A peptide inhibitor derived from p55PIK phosphatidylinositol 3-kinase regulatory subunit: a novel cancer therapy. | |
| | |
MedLine Citation:
|
PMID: 19074847 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
p55PIK, a regulatory subunit of phosphatidylinositol 3-kinase (PI3K), specifically interacts with retinoblastoma protein (Rb) through the unique NH2 terminus of p55PIK, N24. This interaction is critical for cell proliferation and cell cycle progression. To examine p55PIK as a potential target for cancer therapy, we generated an adenovirus expressing N24 (Ad-N24-GFP) and studied its effects on the proliferation of cultured cancer cells, including human colon (HT29) and thyroid (FTC236) cancer cells. Ad-N24-GFP blocked cell proliferation and induced cell cycle arrest in all cancer cell lines tested. N24 induced cell cycle arrest at G0-G1 phase in cell lines that expressed Rb. Interestingly, N24 inhibited cell proliferation by blocking cell cycle transition at both S and G2-M phases in FTC236 cells, which did not express Rb. When Rb was knocked down by short hairpin RNA in HT29 cells, N24 also inhibited cell cycle progression at S and G2-M phases, suggesting that p55PIK regulates cell cycle progression by Rb-dependent and Rb-independent mechanisms. Finally, Ad-N24-GFP markedly decreased the growth of xenograft tumors derived from HT29 and FTC236 cancer cells in athymic nude mice. Our data strongly suggest that N24 peptide is an effective anticancer therapy, which specifically inhibits PI3K signaling pathways mediated by p55PIK. Moreover, they show that the regulatory subunit of an enzyme, in addition to its catalytic subunit, can be an important target for drug development. |
| | |
Authors:
|
Junbo Hu; Xianmin Xia; Aiwu Cheng; Guihua Wang; Xuelai Luo; Michael F Reed; Tito Fojo; Alexis Oetting; Jianping Gong; Paul M Yen |
Related Documents
:
|
3275427 - An analysis of the role of microfilaments in the establishment and maintenance of asymm... 22504647 - Mesenchymal cells regulate retinoic acid receptor-dependent cortical thymic epithelial ... 3896527 - Commitment events in early g1 requirement for the synthesis of dolichol dependent glyco... 6667267 - Specific g1-s phase cell cycle block by beryllium as demonstrated by cytofluorometric a... 18802037 - Isolation of primordial germ cells from differentiating human embryonic stem cells. 12498317 - Investigation of intracellular factors involved in methylmercury toxicity. |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: Molecular cancer therapeutics Volume: 7 ISSN: 1535-7163 ISO Abbreviation: Mol. Cancer Ther. Publication Date: 2008 Dec |
Date Detail:
|
Created Date: 2008-12-16 Completed Date: 2009-02-09 Revised Date: 2010-02-01 |
Medline Journal Info:
|
Nlm Unique ID: 101132535 Medline TA: Mol Cancer Ther Country: United States |
Other Details:
|
Languages: eng Pagination: 3719-28 Citation Subset: IM |
Affiliation:
|
Department of Surgery, Tongji Medical School, Huazhong University of Science and Technology, Wuhan, People's Republic of China. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
1-Phosphatidylinositol 3-Kinase
/
chemistry,
metabolism,
pharmacology*,
physiology* Animals Antineoplastic Agents / pharmacology* Cell Line, Tumor Enzyme Inhibitors / pharmacology Gene Expression Regulation, Enzymologic* Gene Expression Regulation, Neoplastic* Humans Male Mice Mice, Nude Neoplasm Transplantation Neoplasms / drug therapy*, enzymology, metabolism*, pathology Peptide Fragments / chemistry, pharmacology* Peptides / pharmacology* Retinoblastoma Protein / metabolism |
| Chemical | |
Reg. No./Substance:
|
0/Antineoplastic Agents; 0/Enzyme Inhibitors; 0/N24 peptide, human; 0/Peptide Fragments; 0/Peptides; 0/Retinoblastoma Protein; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase; EC 2.7.1.137/PIK3R3 protein, human |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Microsomal antiestrogen-binding site ligands induce growth control and differentiation of human brea...
Next Document: A novel mode of action of YC-1 in HIF inhibition: stimulation of FIH-dependent p300 dissociation fro...