Nabanita S. Datta

Bio: Nabanita S. Datta is an academic researcher from Indian Institute of Technology Kharagpur. The author has contributed to research in topics: Vibration & Beam (structure). The author has an hindex of 19, co-authored 58 publications receiving 2415 citations. Previous affiliations of Nabanita S. Datta include Wayne State University & University of Michigan.

Extracellular Calcium as a Candidate Mediator of Prostate Cancer Skeletal Metastasis

Abstract: Prostate cancer almost exclusively metastasizes to skeletal sites, indicating that the bone provides a favorable microenvironment for its localization and progression. A natural yet understudied factor in bone that could facilitate tumor localization is elevated extracellular calcium ([Ca 2+ ]o). The present study found that elevated [Ca 2+ ]o (2.5 mmol/L) enhanced proliferation of skeletal metastatic prostate cell lines (PC-3 and C4-2B), but not the nonskeletal metastatic, epithelial-derived prostate cell line LNCaP. The proliferative effect of elevated [Ca 2+ ]o was associated with higher expression of the calcium-sensing receptor (CaSR), a heterotrimeric G-protein–coupled receptor that is the predominant cell-surface sensor for [Ca 2+ ]o. Knockdown of the CaSR via RNA interference reduced cell proliferation in vitro and metastatic progression in vivo . CaSR signaling in PC-3 cells was evaluated by measuring the elevated [Ca 2+ ]o-dependent inhibition of cyclic AMP accumulation, induced by either prostaglandin E 2 or forskolin. Elevated [Ca 2+ ]o stabilized expression of cyclin D1, a protein required for cell cycle transition. Furthermore, elevated [Ca 2+ ]o triggered activation of the Akt signaling pathway and enhanced PC-3 cell attachment. Both pertussis toxin (a G-protein inhibitor) and LY294002 (an inhibitor of Akt signaling) reduced cell attachment. These data suggest that elevated [Ca 2+ ]o following increased bone remodeling could facilitate metastatic localization of prostate cancer via the CaSR and the Akt signaling pathway. Taken together, [Ca 2+ ]o is a candidate mediator of prostate cancer bone metastasis. (Cancer Res 2006; 66(18): 9065-73) (Cancer Res 2006; 66(18): 9065-73)

Deficiency of enzymes catalyzing the biosynthesis of glycerol−ether lipids in Zellweger syndrome: a new category of metabolic disease involving the absence of peroxisomes

Abstract: The Zellweger cerebro-hepato-renal syndrome is a genetic disease characterized by the absence of peroxisomes and deficiency of glycerol–ether lipids in several tissues. We measured the activity of dihydroxyacetone phosphate (DHAP) acyltransferase, a peroxisomal enzyme with a major role in ether lipid synthesis, in fibroblasts and leukocytes from patients with Zellweger syndrome. Control skin and amniotic-fluid fibroblasts had normal activity of DHAP acyltransferase (0.28 to 0.3 nmol per minute per milligram of protein), whereas fibroblasts from three patients with Zellweger syndrome had deficient actvity (0.013±0.006 nmol per minute per milligram of protein). The activity of the enzyme in leukocytes and levels of plasmalogens (the major class of cellular glycerol–ether lipids) in erythrocytes were also deficient in a patient, but normal levels of leukocyte enzyme and erythrocyte plasmalogens were found in her parents. Other enzymes of the acyl DHAP pathway exhibited alterations in fibroblasts fro...

Cloning and expression of human deoxycytidine kinase cDNA.

Abstract: Deoxycytidine (dCyd) kinase is required for the phosphorylation of several deoxyribonucleosides and certain nucleoside analogs widely employed as antiviral and chemotherapeutic agents. Detailed analysis of this enzyme has been limited, however, by its low abundance and instability. Using oligonucleotides based on primary amino acid sequence derived from purified dCyd kinase, we have screened T-lymphoblast cDNA libraries and identified a cDNA sequence that encodes a 30.5-kDa protein corresponding to the subunit molecular mass of the purified protein. Expression of the cDNA in Escherichia coli results in a 40-fold increase in dCyd kinase activity over control levels. In dCyd kinase-deficient murine L cells, transfection with dCyd kinase cDNA in a mammalian expression vector produces a 400-fold increase over control in dCyd phosphorylating activity. The expressed enzyme has an apparent Km of 1.0 microM for dCyd and is also capable of phosphorylating dAdo and dGuo. Northern blot analysis reveals a single 2.8-kilobase mRNA expressed in T lymphoblasts at 5- to 10-fold higher levels than in B lymphoblasts, and decreased dCyd kinase mRNA levels are present in T-lymphoblast cell lines resistant to arabinofuranosylcytosine and dideoxycytidine. These findings document that this cDNA encodes the T-lymphoblast dCyd kinase responsible for the phosphorylation of dAdo and dGuo as well as dCyd and arabinofuranosylcytosine.

C-myc overexpression and p53 loss cooperate to promote genomic instability.

Abstract: p53 monitors genomic integrity at the G1 and G2/M cell cycle checkpoints. Cells lacking p53 may show gene amplification as well as the polyploidy or aneuploidy typical of many tumors. The pathways through which this develops, however, are not well defined. We demonstrate here that the combination of p53 inactivation and c-myc overexpression in diploid cells markedly accelerates the spontaneous development of tetraploidy. This is not seen with either N-myc or L-myc. Tetraploidy is accompanied by significantly higher levels of cyclin B and its associated cdc2 kinase activity. Mitotic spindle poisons accelerate the appearance of tetraploidy in cells either lacking functional p53 or overexpressing c-myc whereas the combination is additive. Restoration of p53 function in cells overexpressing c-myc causing rapid apoptosis, indicating that cells yet to become tetraploid have nonetheless suffered irreversible genomic and/or mitotic spindle damage. In the face of normal p53 function, such damage would either be repaired or trigger apoptotis. We propose that loss of p53 and overexpression of c-myc permits the emergence and survival of cells with increasingly severe damage and the eventual development of tetraploidy.

International Union of Pharmacology. XXV. Nomenclature and Classification of Adenosine Receptors

Abstract: Four adenosine receptors have been cloned and characterized from several mammalian species. The receptors are named adenosine A(1), A(2A), A(2B), and A(3). The A(2A) and A(2B) receptors preferably interact with members of the G(s) family of G proteins and the A(1) and A(3) receptors with G(i/o) proteins. However, other G protein interactions have also been described. Adenosine is the preferred endogenous agonist at all these receptors, but inosine can also activate the A(3) receptor. The levels of adenosine seen under basal conditions are sufficient to cause some activation of all the receptors, at least where they are abundantly expressed. Adenosine levels during, e.g., ischemia can activate all receptors even when expressed in low abundance. Accordingly, experiments with receptor antagonists and mice with targeted disruption of adenosine A(1), A(2A), and A(3) expression reveal roles for these receptors under physiological and particularly pathophysiological conditions. There are pharmacological tools that can be used to classify A(1), A(2A), and A(3) receptors but few drugs that interact selectively with A(2B) receptors. Testable models of the interaction of these drugs with their receptors have been generated by site-directed mutagenesis and homology-based modelling. Both agonists and antagonists are being developed as potential drugs.

Matrix metalloproteinases and tumor metastasis

Abstract: Functions of individual matrix metalloproteinases (MMPs) differentially expressed by tumor cells and stromal cells, are finely regulated by their spatial as well as temporal interactions with distinct cellular and extracellular components of the tumor microenvironment and also distant pre-metastatic sites. Certain aspects of MMP involvement in tumor metastasis such as tumor-induced angiogenesis, tumor invasion, and establishment of metastatic foci at the secondary site, have received extensive attention that resulted in an overwhelming amount of experimental and observational data in favor of critical roles of MMPs in these processes. In particular, dependency of tumor angiogenesis on the activity of MMPs, especially that of MMP-9, renders this step possibly the most effective target of synthetic MMP inhibitors. MMP functioning in other stages of metastasis, including the escape of individual tumor cells from the primary tumor, their intravasation, survival in circulation, and extravasation at the secondary site, have not yet received enough consideration, resulting in insufficient or controversial data. The major pieces of evidence that are most compelling and clearly determine the role and involvement of MMPs in the metastatic cascade are provided by molecular genetic studies employing knock-out or transgenic animals and tumor cell lines, modified to overexpress or downregulate a specific MMP. Findings from all of these studies implicate different functional mechanisms for both tumor and stromal MMPs during distinct steps of the metastatic cascade and indicate that MMPs can exhibit pro-metastatic as well as anti-metastatic roles depending on their nature and the experimental setting. This dual function of individual MMPs in metastasis has become a major focus of this review.

Matrix metalloproteinases as modulators of inflammation and innate immunity

Abstract: As their name implies, matrix metalloproteinases are thought to be responsible for the turnover and degradation of the extracellular matrix. However, matrix degradation is neither the sole nor the main function of these proteinases. Indeed, as we discuss here, recent findings indicate that matrix metalloproteinases act on pro-inflammatory cytokines, chemokines and other proteins to regulate varied aspects of inflammation and immunity.

Reflecting on 25 years with MYC

Abstract: Just over 25 years ago, MYC, the human homologue of a retroviral oncogene, was identified. Since that time, MYC research has been intense and the advances impressive. On reflection, it is astonishing how each incremental insight into MYC regulation and function has also had an impact on numerous biological disciplines, including our understanding of molecular oncogenesis in general. Here we chronicle the major advances in our understanding of MYC biology, and peer into the future of MYC research.

Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets

Abstract: Highly pathogenic avian H5N1 influenza A viruses occasionally infect humans, but currently do not transmit efficiently among humans. The viral haemagglutinin (HA) protein is a known host-range determinant as it mediates virus binding to hostspecific cellular receptors 1–3 . Here we assess the molecular changes in HA that would allow a virus possessing subtype H5 HA to be transmissible among mammals. We identified a reassortant H5 HA/H1N1 virus—comprising H5 HA (from an H5N1 virus) with four mutations and the remaining seven gene segments from a 2009 pandemic H1N1 virus—that was capable of droplet transmission in a ferret model. The transmissible H5 reassortant virus preferentially recognized human-type receptors, replicated efficiently in ferrets, caused lung lesions and weight loss, but was not highly pathogenic and did not cause mortality. These results indicate that H5 HA can convert to an HA that supports efficient viral transmission in mammals; however, we do not know whether the four mutations in the H5 HA identified here would render a wholly avian H5N1 virus transmissible. The genetic origin of the remaining seven viral gene segments may also critically contribute to transmissibility in mammals. Nevertheless, as H5N1 viruses continue to evolve and infect humans, receptor-binding variants of H5N1 viruses with pandemic potential, including avian–human reassortant viruses as tested here, may emerge. Our findings emphasize the need to prepare for potential pandemics caused by influenza viruses possessing H5 HA, and will help individuals conducting surveillance in regions with circulating H5N1 viruses to