Alpana Ray

University of Missouri | Mizzou · Department of Veterinary Pathobiology

Besides the involvement of mTOR activity in several cancer conditions, evidence exists that increased total mTOR protein level might be linked to some cancer conditions such as colorectal carcinoma. The increase in total mTOR protein level in colon cancer was found to be associated with enhanced tumor progression and poor prognosis. We found that...

Regulatory mechanism of EGFR/HER1 expression in breast cancer cells involves Ras-mediated activation of SAF-1 Brett M. Havis, Mohamed Alalem, Alpana Ray and Bimal K. Ray Department of Veterinary Pathobiology, University of Missouri, Columbia, MO Tumor microenvironment (TME) plays a critical role in tumor growth, invasion and metastasis. In TME, epi...

The primary function of insulin is viewed as a hormone that controls blood glucose level. However, there is growing evidence that aberrant insulin level and insulin-mediated signaling can lead to cancer development and progression. The insulin-cancer relationship has stemmed from various observational and epidemiological studies, which linked highe...

In the majority of breast cancers, overexpression and hyperactivation of Ras in the tumor microenvironment play significant role in promoting cancer cell growth, angiogenesis, and metastasis. We have previously shown that vascular endothelial growth factor (VEGF) expression in triple negative breast cancer cells is regulated, at least in part, by S...

While breast cancer is considered to be a more easily treatable carcinoma, there are still some forms of the disease that have a poor prognosis due to a high metastatic rate. Successful treatment of breast cancer can be achieved through research on identifying new molecular targets. Bitter melon (BM), a widely used vegetable in Asia, South America...

While breast cancer is considered to be a more easily treatable carcinoma, there are still some forms of the disease that have a poor prognosis due to a high metastatic rate. Successful treatment of breast cancer can be achieved through research on identifying new molecular targets. Bitter melon (BM), a widely used vegetable in Asia, South America...

Osteoarthritis (OA) is a disease that damages the joint tissues and often destroys the cartilage lining of the joint tissue irreversibly. This leads to loss of joint function making movement difficult and crippling the affected individuals. OA primarily affects elderly population and with increasing aging human population in the world it is going t...

There is substantial evidence that metformin, an anti-diabetic biguanide, correlates with improved breast cancer response to chemotherapy. The exact mechanism of metformin's beneficial effect in breast cancer is yet to be fully understood. Metformin inhibits a serine/ threonine kinase called mammalian target of rapamycin (mTOR), which is a central...

Vascular endothelial growth factor (VEGF) is recognized as an important angiogenic factor that promotes angiogenesis in a series of pathological conditions, including cancer, inflammation, and ischemic disorders. We have recently shown that the inflammatory transcription factor SAF-1 is, at least in part, responsible for the marked increase of VEGF...

A disintegrin and metalloprotease domain-containing protein 12 (ADAM12) is up-regulated in many human cancers and promotes cancer metastasis. Increased urinary level of ADAM-12 in breast and bladder cancers correlates with the disease progression. However, the mechanism of its induction in cancer remains less understood. Previously, we reported a Z...

Angiogenesis plays an important role in the tumor growth and metastasis by facilitating increased blood supply and thus fueling unwanted growth factors and nutrients to the growing tumor. Vascular endothelial growth factor (VEGF) is recognized as a multifunctional angiogenic stimulator that stimulates blood vessel formation and endothelial cell sur...

Angiogenesis plays a significant role in cancer by providing increased blood supply to the affected tissues and thus bringing in growth factors, cytokines, and various nutrients for tumor growth. VEGF is the most prominent angiogenic agent that is markedly induced in cancer. Induction of VEGF has been widely studied but as cancer cells are quite ad...

Upregulation of ADAM-12, a novel member of the multifunctional ADAM family of proteins is linked to cancer, arthritis and cardiac hypertrophy. Basal expression of ADAM-12 is very low in adult tissues but rises markedly in response to certain physiological cues, such as during pregnancy in the placenta, during development in neonatal skeletal muscle...

A disintegrin and metalloproteinase-12 (ADAM-12), a member of multifunctional family of proteins, is upregulated in many cancers, including breast, lung, liver, prostate, gastric, and bladder. The multidomain structure, composed of a prodomain, a metalloproteinase, disintegrin-like, epidermal growth factor-like, cysteine-rich and transmembrane doma...

We reported earlier in a guinea pig model that exposure of 2-chloroethyl ethyl sulfide (CEES), a mustard gas analog, causes lung injury associated with the activation of tumor necrosis factor alpha (TNF-alpha), mitogen activated protein kinases (MAPK) signaling, and activator protein-1 (AP-1) transcription factor. Our earlier studies also revealed...

The Cys2His2-type zinc finger transcription factor serum amyloid A activating factor 1 [SAF-1, also known as MAZ (myc-associated zinc finger protein) or Pur-1 (purine binding factor-1)] plays an important role in regulation of a variety of inflammation-responsive genes. An SAF-2 splice variant acting as a negative regulator of SAF-1 was identified...

Previously we determined that inflammation responsive transcription factors AP-1 and SAF-1 synergistically regulate transcriptional induction of the MMP-1 gene. The present study investigated the underlying molecular mechanism of cooperativity between these two different groups of transcription factors. We present evidence that knockdown of SAF-1 b...

Previously we determined that inflammation responsive transcription factors AP-1 and SAF-1 synergistically regulate transcriptional induction of the MMP-1 gene. The present study investigated the underlying molecular mechanism of cooperativity between these two different groups of transcription factors. We present evidence that knockdown of SAF-1 b...

Although the liver is the primary site of cytokine-mediated expression of acute-phase serum amyloid A (SAA) protein, extrahepatic production has also been reported. Besides its role in amyloidosis and lipid homeostasis during the acute-phase, SAA has recently been assumed to contribute to bone and cartilage destruction. However, expression of SAA i...

A number of risk factors including biomechanical stress on the articular cartilage imposed by joint overloading due to obesity, repetitive damage of the joint tissues by injury of the menisci and ligaments, and abnormal joint alignment play a significant role in the onset of osteoarthritis (OA). Genetic predisposition can also lead to the formation...

Vascular endothelial growth factor (VEGF) plays an important role in the pathogenesis of arthritis by promoting angiogenesis in the synovial joint and infiltration of inflammatory cells in the synovial joint. Although ample information has been obtained on the mechanism of VEGF regulation during cancer and hypoxic condition, less is known about the...

Abundantly expressed serum amyloid A (SAA) protein under chronic inflammatory conditions gives rise to insoluble aggregates of SAA derivatives in multiple organs resulting in reactive amyloid A (AA) amyloidosis, a consequence of rheumatoid arthritis, Crohn's disease, ankylosing spondylitis, familial Mediterranean fever, and Castleman's disease. An...

The placenta comprises a highly specialized trophoblast layer, which arises from the embryo and differentiates during embryonic development to perform specialized functions, e.g., synthesis of pregnancy-associated hormones, growth factors and cytokines. As there is no evidence of maternal acute-phase protein transplacental transfer and trophoblast...

Matrix metalloproteinase-1 (MMP-1) has been implicated in the pathogenesis of osteoarthritis (OA) due to its ability to degrade extracellular matrix component of the joint cartilage tissue that cushions the bone from frictional damage. Canine hip dysplasia, a developmental orthopedic disease which results in arthritic condition as is seen in human...

Increased expression of matrix metalloproteinase-9 (MMP-9) by IL-1beta and TNF-alpha is regarded as a key factor in the degradation of cartilage during arthritis. However, the underlying molecular mechanism of this induction process especially in the cells of the joint capsule remains elusive. Chondrocytes and synoviocytes, the resident cells of jo...

Serum amyloid A-activating transcription factor-1 (SAF-1) plays a major role in regulating transcription of several inflammation-responsive genes, including SAA and matrix metalloproteinase-1, that are implicated in the pathogenesis of reactive secondary amyloidosis, atherosclerosis, and arthritis. SAF-1 is a 477-amino acid protein with six zinc fi...

Based on epidemiological and pathological studies, it is becoming increasingly clear that matrix metalloproteinases (MMPs) play an important role in the pathogenesis of atherosclerosis by participating in vascular remodeling, smooth muscle cell migration, and plaque disruption. MMP-14, because of its unique ability to cause pericellular degradation...

The transcription factor serum amyloid A-activating factor-1 (SAF-1) has been identified as a regulator of a number of cellular genes. To assess the pleiotropic role of SAF-1 in vivo, we generated SAF-1 transgenic mice, in which CMV immediate-early promoter was used to direct expression of the SAF-1 transgene in multiple organs. Our study shows tha...

Inflammation-responsive transcription factor, serum amyloid A-activating factor 1 (SAF-1), has been shown to regulate several genes, including serum amyloid A, gamma-fibrinogen, and matrix metalloproteinase 1, whose abnormal expression is associated with the pathogenesis of arthritis, atherosclerosis, and amyloidosis. Prolonged high level expressio...

Serum amyloid A (SAA) activating factor-1 (SAF-1) is an inducible transcription factor that plays a key role in the regulation of several inflammation-responsive genes including SAA and matrix metalloproteinase-1. Increased synthesis of SAA and matrix metalloproteinase-1 is associated with pathogenesis of several diseases including amyloidosis, art...

To identify specific transcription factors that are activated in the cartilage tissue of osteoarthritis (OA) patients and are involved in the expression of matrix metalloproteinase 1 (MMP-1). DNase I footprint and electrophoretic mobility shift assays were performed to identify active elements of the MMP1 promoter and the transcription factors that...

Serum amyloid A-activating factor-1 (SAF-1), a Cys(2)His(2)-type zinc finger transcription factor, regulates inflammation-induced expression of serum amyloid A protein that is linked to the pathogenesis of reactive amyloidosis, rheumatoid arthritis, and atherosclerosis. Here we report the identification of a novel splice variant, SAF-2, of the SAF...

SAF-1, a zinc finger transcription factor, is activated by a number of inflammatory agents, including interleukin-1 (IL-1) and IL-6. It is involved in the cytokine-mediated transcriptional induction of serum amyloid A, an acute-phase plasma protein that is associated with the pathogenesis of reactive amyloidosis, rheumatoid arthritis, and atheroscl...

The serum amyloid A activating factor (SAF) was identified as a family of inducible transcription factors that is activated by many mediators of inflammation. Its activation involves a phosphorylation event, whose mechanism is not fully understood. Here, we show that cAMP treatment of several cell types, including mouse liver-derived BNL CL.2, huma...

Serum amyloid A-activating factor-1 (SAF-1) is a zinc finger transcription factor that is activated by many mediators of inflammation including IL-1, IL-6, and bacterial LPS. However, the mechanism of activation is not fully understood. To identify possible activation partners for SAF-1, we used a yeast two-hybrid system that detected interaction b...

The transcription factor serum amyloid A (SAA)-activating factor (SAF), a family of zinc finger proteins, plays a significant role in the induced expression of the SAA gene. Activity of SAF is regulated by a phosphorylation event involving serine/threonine protein kinase (Ray, A., Schatten, H., and Ray, B. K. (1999) J. Biol. Chem. 274, 4300–4308; R...

Expression of fibrinogen is highly induced during inflammation, and such abnormal expression of this protein is considered as a major cardiovascular risk factor. IL-6 is one of the main mediators of abnormal expression of fibrinogen leading to the pathogenic conditions. Transient transfection and EMSA were performed to investigate the molecular mec...

The serum amyloid A (SAA) protein has been implicated in the pathogenesis of several chronic inflammatory diseases. Its induction mechanism in response to a chronic inflammatory condition was investigated in rabbits following multiple s.c. injections of AgNO3 over a period of 35 days. During unremitting exposure to inflammatory stimulus, a persiste...

The serum amyloid A (SAA) protein has been implicated in the progression and pathogenesis of rheumatoid arthritis through induction of collagenase activity in synovial fibroblast cells that line the joint tissues. We demonstrate that SAA is synergistically induced in synovial cells by interleukin (IL)-1 and IL-6 that are present at significantly hi...

The serum amyloid A (SAA) protein has been implicated in the progression and pathogenesis of rheumatoid arthritis through induction of collagenase activity in synovial fibroblast cells that line the joint tissues. We demonstrate that SAA is synergistically induced in synovial cells by interleukin (IL)-1 and IL-6 that are present at significantly hi...

Minimally modified low-density lipoprotein (MM-LDL) is regarded as a major risk factor for the development of atherosclerosis. In this report, we show that this lipoprotein complex can induce expression of an inflammatory protein, serum amyloid A (SAA), in monocyte/macrophage cells, a key cell type implicated in the pathogenesis of atherosclerosis....

Serum amyloid A (SAA), a plasma protein inducible in response to many inflammatory conditions, is associated with the pathogenesis of several diseases including reactive amyloidosis, rheumatoid arthritis, and atherosclerosis. We have previously reported an element of the SAA promoter, designated SAA-activating sequence (SAS), that is involved in th...

Serum amyloid A (SAA) is a plasma protein that is associated with many inflammatory diseases including amyloidosis, arthritis, and atherosclerosis. SAA level is significantly increased during inflammatory condition, and such abnormal expression of this protein is linked to the pathogenesis of the above-mentioned diseases. A promoter element, design...

Serum amyloid A (SAA) has been linked to atherosclerosis because of its ability to remodel high-density lipoprotein by the depletion of apolipoprotein A1, its ability to bind cholesterol, and its presence in the atherosclerotic plaques of coronary and carotid arteries. In the present study, we investigated the induction mechanism of SAA gene in THP...

Serum amyloid A (SAA) is highly induced during many inflammatory episodes. The induction mechanism in response to turpentine and lipopolysaccharide (LPS), two major inducers of this gene, was investigated. Here we present evidence that although both agents triggered expression, SAA mRNA synthesized in the turpentine-injected rabbit liver is many-fo...

Serum amyloid A (SAA) is a plasma protein which has been associated with several diseases, including amyloidosis, arthritis, and atherosclerosis, and its abnormal expression, particularly in nonhepatic cells, is implicated in the pathogenesis of these diseases. Transfection and DNA-binding studies were performed to investigate the mechanism control...

alpha 1-Antitrypsin (alpha 1-AT) is one of the major proteinase inhibitors in serum. Its primary physiological function is to inhibit neutrophil elastase activity in lung, but it also inhibits other serine proteases including trypsin, chymotrypsin, thrombin, and cathepsin. We have previously reported a novel alpha 1-AT, S-2 isoform, from rabbit tha...

The interleukin-6 (IL-6) gene expression in bovine monocytes is highly induced following bacterial lipopolysaccharide (LPS) stimulation, To identify the promoter element(s) involved in the inducible transcription of IL-6, a 5'-flanking region containing 230 bp of the bovine IL-6 gene was linked to a reporter gene coding for bacterial chloramphenico...

The promoter region of the rabbit serum amyloid A (SAA) gene contains two adjacent C/EBP and one NF-kappa B binding element. Involvement of these elements in SAA gene induction, following lipopolysaccharide (LPS) stimulation of the liver, has been studied by investigating LPS-activated transcription factors and their interaction with the promoter e...

alpha 1-Antitrypsin is a major plasma proteinase inhibitor whose primary function is to control the proteolytic activity of neutrophil elastase that hydrolyzes structural proteins. This protein, in rabbit is expressed as three isoforms designated as F, S-1, and S-2. An inducible form of this protein has been cloned from an acute-phase cDNA library...

Analysis of the regulatory promoter region of the rabbit alpha 1-acid glycoprotein (alpha 1-AGP)-encoding gene revealed the presence of a G + C-rich region that is a potential binding site for the transcription factor Sp1. DNase I footprinting and competition with Sp1-specific wild-type oligodeoxyribonucleotides showed that Sp1 interacts with a tan...

Serum amyloid A (SAA) is a plasma protein whose synthesis is markedly increased in the liver during the inflammatory process. Previous analysis of SAA promoter function implicated the involvement of the CCAAT/enhancer-binding protein (C/EBP) in controlling this process. In this study, using antibodies against three C/EBP isoforms in DNA-binding and...

Transcription of the gene encoding alpha 1-acid glycoprotein is highly induced during acute inflammation which has been previously shown to be mediated by some inducible members of the CCAAT-enhancer-binding (C/EBP) transcription-factor family. In this study, we demonstrate that the involved inducible C/EBP isoforms are C/EBP-beta and C/EBP-delta,...

Transcription of the gene encoding α1-acid glycoprotein is highly induced during acute inflammation which has been previously shown to be mediated by some inducible members of the CCAAT-enhancer-binding (C/EBP) transcription-factor family. In this study, we demonstrate that the involved inducible C/EBP isoforms are C/EBP-β and C/EBP-δ, and together...

To identify the cis-acting DNA sequences responsible for inducible transcription of rabbit alpha 1-acid glycoprotein gene, 5'-flanking region containing 529 bp of this gene and its various 5'-deletions were linked to the reporter gene coding for the bacterial chloramphenicol acetyltransferase (CAT) and analyzed for their ability to confer cytokine-...

To identify the cis-acting DNA sequences responsible for inducible transcription of rabbit 1-acid glycoprotein gene, 5′-flanking region containing 529 bp of this gene and its various 5′-deletions were linked to the reporter gene coding for the bacterial chloramphenicol acetyltransferase (CAT) and analyzed for their ability to confer cytokine-mediat...

Serum amyloid A (SAA) protein synthesis is highly induced in acute inflammatory conditions. Such induction process is primarily regulated at the transcriptional level and large amount of SAA mRNA has been found to accumulate in rabbit liver during acute inflammation. To identify the promoter element(s) involved in inducible transcription of SAA, a...

In an effort to identify regulatory elements of the serum amyloid A (SAA) gene that play a major role in its expression under acute-phase conditions, we studied the expression of a set of chimeric SAA-chloramphenicol acetyltransferase (CAT) plasmids containing a progressively deleted upstream 5' sequence of the SAA gene. Two regulatory regions (-31...

Alpha 1-acid glycoprotein (alpha 1-AGP) is a major acute phase protein that is highly inducible during hepatic acute-phase response. To identify the promoter element(s) required for increased gene transcription under acute condition a 529 bp 5'-flanking region of alpha 1-AGP gene is fused to the chloramphenicol acetyl transferase (CAT) reporter gen...

The gene for rabbit alpha 1 acid glycoprotein (AGP) has been isolated from a lambda EMBL3 genomic DNA library. Isolated clone contains a 12 Kbp fragment of rabbit genomic DNA. Restriction endonuclease mapping has localized the gene within a 4.2 Kbp fragment spanning two EcoRI sites. Southern blot analysis of the rabbit genomic DNA and its compariso...

A genomic DNA clone that encodes serum amyloid A protein has been isolated from a rabbit liver lambda EMBL3 genomic library. Southern blot analysis indicates that the cloned gene is a member of multiple SAA gene family in rabbit. The nucleotide sequence of this DNA shows that the cloned gene corresponds to a SAA cDNA recently isolated from an acute...

Alpha 1-acid glycoprotein (AGP) complementary DNA clone has been isolated from an acute phase rabbit liver library. Complete and full-length nucleotide sequence of this cDNA has been determined. The cDNA contains 35 nucleotides 5' untranslated region followed by 606 nucleotides of coding region and a 112 nucleotides 3' untranslated region. Comparis...

A complementary DNA clone encoding serum amyloid A protein has been isolated from an acute rabbit liver cDNA library. Complete nucleotide sequence analysis reveals that the cloned gene contains a 24 bases 5' untranslated region, 369 bases coding region and a 106 bases 3' untranslated region. Primer extension analysis indicates that the full-length...

Intracellular growth of protozoan parasite Babesia bovis has been followed to study the effect of some chemical agents on growth regulation. Using an in vitro parasite culture system we present evidence that the normal growth of the parasite is dependent upon available calcium and a Ca2(+)-binding protein, calmodulin, because sequestration of eithe...

Translation rates were determined for host and virus mRNAs in reovirus-infected SC-1 cells in hypertonic medium. The effect of low doses of cycloheximide on these translation rates was also measured. The results show that hypertonicity selectively stimulates viral translation relative to host translation. Moreover, in hypertonic medium, host transl...