Dataset Information

Anti-caveolin-1 antibodies as anti-prostate cancer therapeutics.

ABSTRACT: Caveolae are critical cell surface structures important in coordinated cell signaling and endocytosis. One of the major proteins of caveolae is caveolin 1 (Cav-1). Cellular levels of Cav-1 are associated with cancer progression. In prostate cancer cells, levels of Cav-1 are positively correlated with tumor progression and metastasis. Cav-1 can be secreted by prostate cancer cells into the microenvironment and triggers proliferation and anti-apoptosis of the tumor and tumor endothelial cells. Clinical studies have shown increased serum Cav-1 levels in patients with poor prognosis. In tissue culture and animal model experiments, blocking secreted Cav-1 by polyclonal antibodies inhibits tumor cell growth. Cav-1 is therefore a potential therapeutic target for prostate cancer treatment. In this study, we used Cav-1 knock-out mice as hosts to produce monoclonal anti-Cav-1 antibodies. A total of 11 hybridoma cell lines were selected for their ability to produce antibodies that bound GST-Cav-1 but not GST on glutathione-coated ELISA plates. Further screening with ELISAs using GST-Cav-1 fragments on GSH-coated plates classified these antibodies into four groups: N1-31 with five antibodies binds the far N-terminus between amino acids 1 and 31; N32-80 with three antibodies binds between amino acids 32 and 80; CSD with two antibodies potentially bind the scaffolding domain (amino acids 80-101); and Cav-1-C with 1 antibody binds parts of the C-terminal half. Binding affinities (Kd) of these antibodies to soluble Cav-1 ranged from 10(-11) to 10(-8) M. Binding competition experiments revealed that these antibodies recognized a total of six different epitopes on Cav-1. Potency of these antibodies to neutralize Cav-1-mediated signaling pathways in cultured cells and in animal models will be tested. A selected monoclonal antibody will then be humanized and be further developed into a potential anti-prostate cancer therapeutic.

SUBMITTER: Kuo SR

PROVIDER: S-EPMC3326273 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Anti-caveolin-1 antibodies as anti-prostate cancer therapeutics.

Kuo Shu-Ru SR Tahir Salahaldin A SA Park Sanghee S Thompson Timothy C TC Coffield Scott S Frankel Arthur E AE Liu Jen-Sing JS

Hybridoma (2005) 20120401 2

Caveolae are critical cell surface structures important in coordinated cell signaling and endocytosis. One of the major proteins of caveolae is caveolin 1 (Cav-1). Cellular levels of Cav-1 are associated with cancer progression. In prostate cancer cells, levels of Cav-1 are positively correlated with tumor progression and metastasis. Cav-1 can be secreted by prostate cancer cells into the microenvironment and triggers proliferation and anti-apoptosis of the tumor and tumor endothelial cells. Cli ...[more]

PMID: 22509911

Similar Datasets

Project description:Cyclin Dependent Kinase 9 (CDK9) is one of the most important transcription regulatory members of the CDK family. In conjunction with its main cyclin partner-Cyclin T1, it forms the Positive Transcription Elongation Factor b (P-TEFb) whose primary function in eukaryotic cells is to mediate the positive transcription elongation of nascent mRNA strands, by phosphorylating the S2 residues of the YSPTSPS tandem repeats at the C-terminus domain (CTD) of RNA Polymerase II (RNAP II). To aid in this process, P-TEFb also simultaneously phosphorylates and inactivates a number of negative transcription regulators like 5,6-dichloro-1-β-D-ribofuranosylbenzimidazole (DRB) Sensitivity-Inducing Factor (DSIF) and Negative Elongation Factor (NELF). Significantly enhanced activity of CDK9 is observed in multiple cancer types, which is universally associated with significantly shortened Overall Survival (OS) of the patients. In these cancer types, CDK9 regulates a plethora of cellular functions including proliferation, survival, cell cycle regulation, DNA damage repair and metastasis. Due to the extremely critical role of CDK9 in cancer cells, inhibiting its functions has been the subject of intense research, resulting the development of multiple, increasingly specific small-molecule inhibitors, some of which are presently in clinical trials. The search for newer generation CDK9 inhibitors with higher specificity and lower potential toxicities and suitable combination therapies continues. In fact, the Phase I clinical trials of the latest, highly specific CDK9 inhibitor BAY1251152, against different solid tumors have shown good anti-tumor and on-target activities and pharmacokinetics, combined with manageable safety profile while the phase I and II clinical trials of another inhibitor AT-7519 have been undertaken or are undergoing. To enhance the effectiveness and target diversity and reduce potential drug-resistance, the future of CDK9 inhibition would likely involve combining CDK9 inhibitors with inhibitors like those against BRD4, SEC, MYC, MCL-1 and HSP90.

Dataset Information

Anti-caveolin-1 antibodies as anti-prostate cancer therapeutics.

Publications

Anti-caveolin-1 antibodies as anti-prostate cancer therapeutics.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets