Biomaterial Database

Nuclear p21-activated kinase 1 in breast cancer packs off tamoxifen sensitivity. 2006

Suresh K Rayala, and Poonam R Molli, and Rakesh Kumar

Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Texas 77030, USA.

There is significant clinical interest in the factors that influence the development of tamoxifen resistance in estrogen receptor-alpha (ER-alpha)-positive breast cancers. Recent studies suggest that in ER-positive breast tumor cells, elevated protein levels, and in particular, nuclear localization of p21-activated kinase 1 (PAK1), is associated with the progressive limitation of tamoxifen sensitivity. These phenotypic effects of PAK1 in model systems are mechanistically linked with the ability of PAK1 to phosphorylate ER-alpha on serine 305 and subsequent secondary activation of serine 118. These findings prompt further investigation of how nuclear signaling by PAK1 may affect estrogen's action and whether tamoxifen resistance might be prevented or reversed by PAK1 inhibition.

UI	MeSH Term	Description	Entries
D001943	Breast Neoplasms	Tumors or cancer of the human BREAST.	Breast Cancer,Breast Tumors,Cancer of Breast,Breast Carcinoma,Cancer of the Breast,Human Mammary Carcinoma,Malignant Neoplasm of Breast,Malignant Tumor of Breast,Mammary Cancer,Mammary Carcinoma, Human,Mammary Neoplasm, Human,Mammary Neoplasms, Human,Neoplasms, Breast,Tumors, Breast,Breast Carcinomas,Breast Malignant Neoplasm,Breast Malignant Neoplasms,Breast Malignant Tumor,Breast Malignant Tumors,Breast Neoplasm,Breast Tumor,Cancer, Breast,Cancer, Mammary,Cancers, Mammary,Carcinoma, Breast,Carcinoma, Human Mammary,Carcinomas, Breast,Carcinomas, Human Mammary,Human Mammary Carcinomas,Human Mammary Neoplasm,Human Mammary Neoplasms,Mammary Cancers,Mammary Carcinomas, Human,Neoplasm, Breast,Neoplasm, Human Mammary,Neoplasms, Human Mammary,Tumor, Breast
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013629	Tamoxifen	One of the SELECTIVE ESTROGEN RECEPTOR MODULATORS with tissue-specific activities. Tamoxifen acts as an anti-estrogen (inhibiting agent) in the mammary tissue, but as an estrogen (stimulating agent) in cholesterol metabolism, bone density, and cell proliferation in the ENDOMETRIUM.	ICI-46,474,ICI-46474,ICI-47699,Nolvadex,Novaldex,Soltamox,Tamoxifen Citrate,Tomaxithen,Zitazonium,Citrate, Tamoxifen,ICI 46,474,ICI 46474,ICI 47699,ICI46,474,ICI46474,ICI47699
D017346	Protein Serine-Threonine Kinases	A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.	Protein-Serine-Threonine Kinases,Serine-Threonine Protein Kinase,Serine-Threonine Protein Kinases,Protein-Serine Kinase,Protein-Serine-Threonine Kinase,Protein-Threonine Kinase,Serine Kinase,Serine-Threonine Kinase,Serine-Threonine Kinases,Threonine Kinase,Kinase, Protein-Serine,Kinase, Protein-Serine-Threonine,Kinase, Protein-Threonine,Kinase, Serine-Threonine,Kinases, Protein Serine-Threonine,Kinases, Protein-Serine-Threonine,Kinases, Serine-Threonine,Protein Kinase, Serine-Threonine,Protein Kinases, Serine-Threonine,Protein Serine Kinase,Protein Serine Threonine Kinase,Protein Serine Threonine Kinases,Protein Threonine Kinase,Serine Threonine Kinase,Serine Threonine Kinases,Serine Threonine Protein Kinase,Serine Threonine Protein Kinases
D054462	p21-Activated Kinases	A family of serine-threonine kinases that bind to and are activated by MONOMERIC GTP-BINDING PROTEINS such as RAC GTP-BINDING PROTEINS and CDC42 GTP-BINDING PROTEIN. They are intracellular signaling kinases that play a role the regulation of cytoskeletal organization.	PAK Kinase,p21-Activated Kinase,Oligophrenin-3,PAK Kinases,PAK-1 Kinase,PAK-2 Kinase,PAK1 Kinase,PAK2 Kinase,PAK3 Kinase,PAK65,Serine-Threonine-Protein Kinase PAK 1,Serine-Threonine-Protein Kinase PAK 3,alpha p21-Activated Kinase,alpha-PAK,beta p21-Activated Kinase,beta-PAK,gamma-PAK,p21-Activated Kinase 1,p21-Activated Kinase 2,p21-Activated Kinase 3,p65(PAK),p65PAK Protein,Kinase, PAK,Kinase, p21-Activated,Kinases, PAK,Kinases, p21-Activated,Oligophrenin 3,PAK 1 Kinase,PAK 2 Kinase,Serine Threonine Protein Kinase PAK 1,Serine Threonine Protein Kinase PAK 3,alpha p21 Activated Kinase,beta p21 Activated Kinase,gamma PAK,p21 Activated Kinase,p21 Activated Kinase 1,p21 Activated Kinase 2,p21 Activated Kinase 3,p21 Activated Kinases,p21-Activated Kinase, beta
D018931	Antineoplastic Agents, Hormonal	Antineoplastic agents that are used to treat hormone-sensitive tumors. Hormone-sensitive tumors may be hormone-dependent, hormone-responsive, or both. A hormone-dependent tumor regresses on removal of the hormonal stimulus, by surgery or pharmacological block. Hormone-responsive tumors may regress when pharmacologic amounts of hormones are administered regardless of whether previous signs of hormone sensitivity were observed. The major hormone-responsive cancers include carcinomas of the breast, prostate, and endometrium; lymphomas; and certain leukemias. (From AMA Drug Evaluations Annual 1994, p2079)	Hormonal Antineoplastic Agents,Antineoplastic Drugs, Hormonal,Antineoplastic Hormonal Agents,Antineoplastic Hormonal Drugs,Antineoplastics, Hormonal,Hormonal Agents, Antineoplastic,Hormonal Antineoplastic Drugs,Hormonal Antineoplastics,Agents, Antineoplastic Hormonal,Drugs, Antineoplastic Hormonal,Hormonal Drugs, Antineoplastic