ABSTRACT
Nuclear orphan receptor NR4A1 exerts an essential tumor suppressor function in aggressive lymphomas. In this study, we investigated the hypothesized contribution of the related NR4A family member NR4A3 to lymphomagenesis. In aggressive lymphoma patients, low expression of NR4A3 was associated with poor survival. Ectopic expression or pharmacological activation of NR4A3 in lymphoma cell lines led to a significantly higher proportion of apoptotic cells. In a mouse NSG xenograft model of lymphoma (stably transduced SuDHL4 cells), NR4A3 expression abrogated tumor growth, compared with vector control and uninduced cells that formed massive tumors. Transcript analysis of four different aggressive lymphoma cell lines overexpressing either NR4A3 or NR4A1 revealed that apoptosis was driven similarly by induction of BAK, Puma, BIK, BIM, BID, and Trail. Overall, our results showed that NR4A3 possesses robust tumor suppressor functions of similar impact to NR4A1 in aggressive lymphomas. Cancer Res; 77(9); 2375-86. ©2017 AACR.
Subject(s)
Carcinogenesis/genetics , Cell Proliferation/genetics , DNA-Binding Proteins/genetics , Lymphoma/genetics , Receptors, Steroid/genetics , Receptors, Thyroid Hormone/genetics , Animals , Apoptosis/genetics , Cell Line, Tumor , DNA-Binding Proteins/biosynthesis , Disease-Free Survival , Female , Gene Expression Regulation, Neoplastic , Humans , Kaplan-Meier Estimate , Lymphoma/pathology , Male , Mice , Receptors, Steroid/biosynthesis , Receptors, Thyroid Hormone/biosynthesis , Xenograft Model Antitumor AssaysABSTRACT
Intermolecular interactions within living organisms have been found to occur not as individual independent events but as a part of a collective array of interconnected events. The problem of the emergence of this collective dynamics and of the correlated biocommunication therefore arises. In the present paper we review the proposals given within the paradigm of modern molecular biology and those given by some holistic approaches to biology. In recent times, the collective behavior of ensembles of microscopic units (atoms/molecules) has been addressed in the conceptual framework of Quantum Field Theory. The possibility of producing physical states where all the components of the ensemble move in unison has been recognized. In such cases, electromagnetic fields trapped within the ensemble appear. In the present paper we present a scheme based on Quantum Field Theory where molecules are able to move in phase-correlated unison among them and with a self-produced electromagnetic field. Experimental corroboration of this scheme is presented. Some consequences for future biological developments are discussed.
ABSTRACT
On May 11, 2008 the German biophysicist Professor Fritz-Albert Popp will celebrate his 70th birthday. This is a welcome occasion to pay tribute to the scientific achievements and human qualities of a scientist whose merits as one of the founders of biophotonics and as a pioneer of quantum biophysics increasingly find appreciation internationally.