Chemical Kinetic Method for Active-Site Quantification in Fe-N-C Catalysts and Correlation with Molecular Probe and Spectroscopic Site-Counting Methods.

Mononuclear Fe ions ligated by nitrogen (FeNx) dispersed on nitrogen-doped carbon (Fe-N-C) serve as active centers for electrocatalytic O2 reduction and thermocatalytic aerobic oxidations. Despite their promise as replacements for precious metals in a variety of practical applications, such as fuel cells, the discovery of new Fe-N-C catalysts has relied primarily on empirical approaches. In this context, the development of quantitative structure-reactivity relationships and benchmarking of catalysts prepared by different synthetic routes and by different laboratories would be facilitated by the broader adoption of methods to quantify atomically dispersed FeNx active centers. In this study, we develop a kinetic probe reaction method that uses the aerobic oxidation of a model hydroquinone substrate to quantify the density of FeNx centers in Fe-N-C catalysts. The kinetic method is compared with low-temperature Mössbauer spectroscopy, CO pulse chemisorption, and electrochemical reductive stripping of NO derived from NO2- on a suite of Fe-N-C catalysts prepared by diverse routes and featuring either the exclusive presence of Fe as FeNx sites or the coexistence of aggregated Fe species in addition to FeNx. The FeNx site densities derived from the kinetic method correlate well with those obtained from CO pulse chemisorption and Mössbauer spectroscopy. The broad survey of Fe-N-C materials also reveals the presence of outliers and challenges associated with each site quantification approach. The kinetic method developed here does not require pretreatments that may alter active-site distributions or specialized equipment beyond reaction vessels and standard analytical instrumentation.

9-Borafluorenes: Synthesis, Properties, and Reactivity.

This review covers all aspects of 9-borafluorene chemistry, from the first attempted synthesis in 1960 to the present. This class of molecules consists of a tricyclic system featuring a central antiaromatic BC4 ring with two fused arene groups. The synthetic routes to all 9-borafluorenes and their adducts are presented. The Lewis acidity and photophysical properties outlined demonstrate potential utility as sensors and in electronic materials. The reactivity of borafluorenes reveals their prospects as reagents for the synthesis of other boron-containing molecules. The appealing traits of 9-borafluorenes have stimulated investigations into analogues that bear different aromatic groups fused to the central BC4 ring. Finally, we offer our views on the challenges and future of borafluorene chemistry.

Pharmacogenomic Profiling of Pediatric Patients on Psychotropic Medications in an Emergency Department.

OBJECTIVE: The aim of the study was to evaluate the ability of a combinatorial pharmacogenomic test to predict medication blood levels and relative clinical improvements in a selected pediatric population. METHODS: This study enrolled patients between ages 3 to 18 years who presented to a pediatric emergency department with acute psychiatric, behavioral, or mental health crisis and/or concerns, and had previously been prescribed psychotropic medications. Patients received combinatorial pharmacogenomic testing with medications categorized according to gene-drug interactions (GDIs); medications with a GDI were considered "incongruent," and medications without a GDI were considered "congruent." Blood levels for escitalopram, fluoxetine, aripiprazole, and clonidine were evaluated according to level of GDI. Relative clinical improvements in response to the prescribed psychotropic medications were measured using a parent-rated Clinical Global Impression of Improvement (CGI-I) assessment, where lower scores corresponded with greater improvement. RESULTS: Of the 100 patients enrolled, 73% reported taking ≥1 incongruent medication. There was no significant difference in CGI-I scores between patients prescribed congruent versus incongruent medications (3.37 vs 3.68, P = 0.343). Among patients who presented for depression or suicidal ideation, those prescribed congruent medications had significantly lower CGI-I scores compared with those taking incongruent medications ( P = 0.036 for depression, P = 0.018 for suicidal ideation). There was a significant association between medication GDI and blood levels for aripiprazole (n = 15, P = 0.01) and escitalopram (n = 10, P = 0.01). CONCLUSIONS: Our preliminary findings suggest that combinatorial pharmacogenomic testing can predict medication blood levels and relative outcomes based on medication congruency in children presenting to an emergency department with acute psychiatric/behavioral crises. Additional studies will be needed to confirm these findings.

Molecular Catalyst Synthesis Strategies to Prepare Atomically Dispersed Fe-N-C Heterogeneous Catalysts.

We report a strategy to integrate atomically dispersed iron within a heterogeneous nitrogen-doped carbon (N-C) support, inspired by routes for metalation of molecular macrocyclic iron complexes. The N-C support, derived from pyrolysis of a ZIF-8 metal-organic framework, is metalated via solution-phase reaction with FeCl2 and tributyl amine, as a Brønsted base, at 150 °C. Fe active sites are characterized by 57Fe Mössbauer spectroscopy and aberration-corrected scanning transmission electron microscopy. The site density can be increased by selective removal of Zn2+ ions from the N-C support prior to metalation, resembling the transmetalation strategy commonly employed for the preparation of molecular Fe-macrocycles. The utility of this approach is validated by the higher catalytic rates (per total Fe) of these materials relative to established Fe-N-C catalysts, benchmarked using an aerobic oxidation reaction.

Histological variation of early stage atherosclerotic lesions in baboons after prolonged challenge with high-cholesterol, high-fat diet.

INTRODUCTION: The baboon is a well-characterized model of human early stage atherosclerosis. However, histological and morphological changes involved in atherogenesis in baboons are not known. Previously, we challenged baboons with a high-cholesterol, high-fat diet for two years and observed fatty streak and plaque lesions in iliac arteries (RCIA). METHODS: We evaluated histological and morphological changes of baboon arterial lesions and control arteries. In addition, we evaluated the vascular expression of CD68 and SMαA markers with progression of atherosclerosis. RESULTS: We observed changes that correlated with extent of atherosclerosis, including increased maximum intimal thickness. We demonstrated at molecular level the infiltration of smooth muscle cells and macrophages into the intimal layer. Further, we observed histological and morphological discordancy between the affected and adjacent areas of the same RCIA. CONCLUSION: Atherogenesis in baboons is accompanied by histological, morphological, and molecular changes, as in humans, providing insights to evaluate the mechanisms underlying early stage atherosclerosis in target tissues.

Characterization of Young Children Presenting to the Emergency Department for Mental Health Complaints.

OBJECTIVES: From 2011 to 2015, psychiatric emergency department visits among youth in the United States increased 28% and psychiatric visits made up 10% of all pediatric emergency department (ED) visits. Previous research has focused on adolescent mental health, with little characterization of children 10 years of age and younger with mental health complaints. The primary objective of this study was to describe these children who presented to a pediatric ED for mental health complaints in terms of demographics and psychosocial factors. METHODS: One researcher reviewed medical records of children 10 years and younger who presented to the Children's of Alabama ED between January 1, 2016 and May 31, 2016 with a mental health-related chief complaint. Patient data were then categorized based on demographic information, characteristics of the ED visit, and medical and social history. Descriptive analyses were run using SAS version 9.4. RESULTS: In total, 222 patients 10 years and younger were seen between January 1 and May 31, 2016. This age group makes up 20% of all of the children seen in the ED for mental health-related complaints. Patients were 73% male (n = 162) and ages 3 to 10 years, with a mean age of 7.8 years. Patients were 55% white (n = 122), 42% African American (n = 94), 1% Hispanic (n = 2), and 1% other ethnicity (n = 3). Patients' insurance coverage was 76% Medicaid (n = 168), 18% private insurance (n = 39), and 6% uninsured (n = 14). Of the 219 patients treated in the ED (3 left without treatment), 45% of patients were admitted (n = 100). Univariate analyses showed increased odds of admission for children with 3 or more prior psychiatric diagnoses (odds ratio [OR] 2.33, P = 0.03), a family history of psychiatric illness (OR 2.53, P < 0.01), history of any previous psychiatric care (OR 2.61, P = 0.01), a history of trauma (OR 1.84, P = 0.03), and a chief complaint of suicidal ideation (OR 1.54, P < 0.01). Analyses showed a decreased odds of admission for children referred to the ED by their school (OR -1.12, P < 0.01). CONCLUSIONS: The pediatric ED sees a significant number of children ages 10 years and younger for mental health-related complaints. Nearly half of these children were admitted for psychiatric care. Several factors were found to predict admission, which reflect psychosocial influences. These psychosocial factors are important targets for intervention both in the ED and in the community.

Double-negative (CD27-IgD-) B cells are expanded in NSCLC and inversely correlate with affinity-matured B cell populations.

BACKGROUND: The presence of B cells in early stage non-small cell lung cancer (NSCLC) is associated with longer survival, however, the role these cells play in the generation and maintenance of anti-tumor immunity is unclear. B cells differentiate into a variety of subsets with differing characteristics and functions. To date, there is limited information on the specific B cell subsets found within NSCLC. To better understand the composition of the B cell populations found in NSCLC we have begun characterizing B cells in lung tumors and have detected a population of B cells that are CD79A+CD27-IgD-. These CD27-IgD- (double-negative) B cells have previously been characterized as unconventional memory B cells and have been detected in some autoimmune diseases and in the elderly population but have not been detected previously in tumor tissue. METHODS: A total of 15 fresh untreated NSCLC tumors and 15 matched adjacent lung control tissues were dissociated and analyzed by intracellular flow cytometry to detect the B cell-related markers CD79A, CD27 and IgD. All CD79A+ B cells subsets were classified as either naïve (CD27-IgD+), affinity-matured (CD27+IgD-), early memory/germinal center cells (CD27+IgD+) or double-negative B cells (CD27-IgD-). Association of double-negative B cells with clinical data including gender, age, smoking status, tumor diagnosis and pathologic differentiation status were also examined using the logistic regression analysis for age and student's t-test for all other variables. Associations with other B cell subpopulations were examined using Spearman's rank correlation. RESULTS: We observed that double-negative B cells were frequently abundant in lung tumors compared to normal adjacent controls (13 out of 15 cases), and in some cases made up a substantial proportion of the total B cell compartment. The presence of double-negative cells was also found to be inversely related to the presence of affinity-matured B cells within the tumor, Spearman's coefficient of - 0.76. CONCLUSIONS: This study is the first to observe the presence of CD27-IgD- double-negative B cells in human NSCLC and that this population is inversely correlated with traditional affinity-matured B cell populations.

Deoxycholic acid mediates non-canonical EGFR-MAPK activation through the induction of calcium signaling in colon cancer cells.

Obesity and a western diet have been linked to high levels of bile acids and the development of colon cancer. Specifically, increased levels of the bile acid deoxycholic acid (DCA), an established tumor promoter, has been shown to correlate with increased development of colorectal adenomas and progression to carcinoma. Herein we investigate the mechanism by which DCA leads to EGFR-MAPK activation, a candidate mechanism by which DCA may promote colorectal tumorigenesis. DCA treated colon cancer cells exhibited strong and prolonged activation of ERK1/2 when compared to EGF treatment alone. We also showed that DCA treatment prevents EGFR degradation as opposed to the canonical EGFR recycling observed with EGF treatment. Moreover, the combination of DCA and EGF treatment displayed synergistic activity, suggesting DCA activates MAPK signaling in a non-canonical manner. Further evaluation showed that DCA treatment increased intracellular calcium levels and CAMKII phosphorylation, and that blocking calcium with BAPTA-AM abrogated MAPK activation induced by DCA, but not by EGF. Finally we showed that DCA-induced CAMKII leads to MAPK activation through the recruitment of c-Src. Taken together, we demonstrated that DCA regulates MAPK activation through calcium signaling, an alternative mechanism not previously recognized in human colon cancer cells. Importantly, this mechanism allows for EGFR to escape degradation and thus achieve a constitutively active state, which may explain its tumor promoting effects.

Key Strategies for Building Research Capacity of University Faculty Members.

Universities are under pressure to increase external research funding, and some federal agencies offer programs to expand research capacity in certain kinds of institutions. However, conflicts within faculty roles and other aspects of university operations influence the effectiveness of particular strategies for increasing research activity. We review conventional approaches to increasing research, focusing on outcomes for individual faculty members and use one federally-funded effort to build cancer-related research capacity at a public university as an example to explore the impact of various strategies on research outcomes. We close with hypotheses that should be tested in future formal studies.

Inactivation of Adenomatous Polyposis Coli Reduces Bile Acid/Farnesoid X Receptor Expression through Fxr gene CpG Methylation in Mouse Colon Tumors and Human Colon Cancer Cells.

BACKGROUND: The farnesoid X receptor (FXR) regulates bile acid (BA) metabolism and possesses tumor suppressor functions. FXR expression is reduced in colorectal tumors of subjects carrying inactivated adenomatous polyposis coli (APC). Identifying the mechanisms responsible for this reduction may offer new molecular targets for colon cancer prevention. OBJECTIVE: We investigated how APC inactivation influences the regulation of FXR expression in colonic mucosal cells. We hypothesized that APC inactivation would epigenetically repress nuclear receptor subfamily 1, group H, member 4 (FXR gene name) expression through increased CpG methylation. METHODS: Normal proximal colonic mucosa and normal-appearing adjacent colonic mucosa and colon tumors were collected from wild-type C57BL/6J and Apc-deficient (Apc(Min) (/+)) male mice, respectively. The expression of Fxr, ileal bile acid-binding protein (Ibabp), small heterodimer partner (Shp), and cyclooxygenase-2 (Cox-2) were determined by real-time polymerase chain reaction. In both normal and adjacent colonic mucosa and colon tumors, we measured CpG methylation of Fxr in bisulfonated genomic DNA. In vitro, we measured the impact of APC inactivation and deoxycholic acid (DCA) treatment on FXR expression in human colon cancer HCT-116 cells transfected with silencing RNA for APC and HT-29 cells carrying inactivated APC. RESULTS: In Apc(Min) (/+) mice, constitutive CpG methylation of the Fxrα3/4 promoter was linked to reduced (60-90%) baseline Fxr, Ibabp, and Shp and increased Cox-2 expression in apparently normal adjacent mucosa and colon tumors. Apc knockdown in HCT-116 cells increased cellular myelocytomatosis (c-MYC) and lowered (∼50%) FXR expression, which was further reduced (∼80%) by DCA. In human HCT-116 but not HT-29 colon cancer cells, DCA induced FXR expression and lowered CpG methylation of FXR. CONCLUSIONS: We conclude that the loss of APC function favors the silencing of FXR expression through CpG hypermethylation in mouse colonic mucosa and human colon cells, leading to reduced expression of downstream targets (SHP, IBABP) involved in BA homeostasis while increasing the expression of factors (COX-2, c-MYC) that contribute to inflammation and colon cancer.

Comparative analysis of 14-3-3 isoform expression and epigenetic alterations in colorectal cancer.

BACKGROUND: The 14-3-3 family is a group of intracellular proteins found in all eukaryotic organisms. Humans have seven isoforms that serve as scaffolds to promote interactions of regulatory phospho-proteins involved in many vital cellular processes and previous studies have shown that disturbances in native 14-3-3 levels can contribute significantly to the development of various cancers. METHODS: DNA and RNA was extracted from frozen tissue samples collected by the Human Cooperative Tissue Network. RNA samples were reverse transcribed and subjected to qRT-PCR analysis using fluorescently labelled probes. Genomic DNA was treated with bisulfite and cloned into bacterial vectors for subsequent high-resolution sequencing. Mammalian NIH3T3 cells were transformed with 14-3-3 eta and Ras expression vectors synthesized from cDNA. Colonies were counted and transforming capability assessed after 21 days of growth. Cell lysates were analyzed by western blot to verify protein expression. RESULTS: Here we examined normal and cancerous 14-3-3 expression levels of all seven isoforms in a cohort of sporadic colorectal adenocarcinomas and in a group of tumors and their matched normals using qRT-PCR analysis. We found a statistically significant decrease in the levels of 14-3-3 sigma, eta, and zeta observed among adenocarcinomas compared to normal tissue. A parallel analysis of microarray data from the TCGA dataset confirmed that expression of sigma and eta were down-regulated in colon tumors. To explore the mechanisms behind 14-3-3 expression changes, we examined the methylation status of the sigma, eta, and zeta gene promoters in selected samples. Our data identified novel CpG methylation sites in the eta promoter consistent with epigenetic silencing of both 14-3-3 sigma and eta isoforms during colon tumorigenesis. Because epigenetic silencing is the hallmark of a tumor suppressor we tested eta in focus formation assays and found that it is capable of suppressing ras-induced transformation of NIH3T3 cells. CONCLUSION: To our knowledge, this is the first study to identify the 14-3-3 eta gene as a tumor suppressor and that its expression is suppressed in colon tumors by DNA hypermethylation. These data suggest a link between 14-3-3 expression levels and the development of colon cancers.

Differential regulation of EGFR-MAPK signaling by deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA) in colon cancer.

A high-fat diet coincides with increased levels of bile acids. This increase in bile acids, particularly deoxycholic acid (DCA), has been strongly associated with the development of colon cancer. Conversely, ursodeoxycholic acid (UDCA) may have chemopreventive properties. Although structurally similar, DCA and UDCA present different biological and pathological effects in colon cancer progression. The differential regulation of cancer by these two bile acids is not yet fully understood. However, one possible explanation for their diverging effects is their ability to differentially regulate signaling pathways involved in the multistep progression of colon cancer, such as the epidermal growth factor receptor (EGFR)-mitogen-activated protein kinase (MAPK) pathway. This review will examine the biological effects of DCA and UDCA on colon cancer development, as well as the diverging effects of these bile acids on the oncogenic signaling pathways that play a role in colon cancer development, with a particular emphasis on bile acid regulation of the EGFR-MAPK pathway.

Activation of phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) signaling and the consequent induction of transformation by overexpressed 14-3-3γ protein require specific amino acids within 14-3-3γ N-terminal variable region II.

Members of the 14-3-3 superfamily regulate numerous cellular functions by binding phosphoproteins. The seven human isoforms (and the myriad of other eukaryotic 14-3-3 proteins) are highly conserved in amino acid sequence and secondary structure, yet there is abundant evidence that the various isoforms manifest disparate as well as common functions. Several of the human 14-3-3 isoforms are dysregulated in certain cancers and thus have been implicated in oncogenesis; experimentally, 14-3-3γ behaves as an oncogene, whereas 14-3-3σ acts as a tumor suppressor. In this study, we sought to localize these opposing phenotypes to specific regions of the two isoforms and then to individual amino acids therein. Using a bioinformatics approach, six variable regions (VRI-VRVI) were identified. Using this information, two sets of constructs were created in which N-terminal portions (including either VRI-IV or only VRI and VRII) of 14-3-3γ and 14-3-3σ were swapped; NIH3T3 cells overexpressing the four chimeric proteins were tested for transformation activity (focus formation, growth in soft agar) and activation of PI3K and MAPK signaling. We found that the specific phenotypes of 14-3-3γ are associated with the N-terminal 40 amino acids (VRI and VRII); in like fashion, VRI and VRII of 14-3-3σ dictated its tumor suppressor function. Using individual amino acid substitutions within the 14-3-3γ VRII, we identified two residues required for and two contributing to the γ-specific phenotypes. Our observations suggest that isoform-specific phenotypes are dictated by a relatively few amino acids within variable regions.

Development and evaluation of a biomedical search engine using a predicate-based vector space model.

Although biomedical information available in articles and patents is increasing exponentially, we continue to rely on the same information retrieval methods and use very few keywords to search millions of documents. We are developing a fundamentally different approach for finding much more precise and complete information with a single query using predicates instead of keywords for both query and document representation. Predicates are triples that are more complex datastructures than keywords and contain more structured information. To make optimal use of them, we developed a new predicate-based vector space model and query-document similarity function with adjusted tf-idf and boost function. Using a test bed of 107,367 PubMed abstracts, we evaluated the first essential function: retrieving information. Cancer researchers provided 20 realistic queries, for which the top 15 abstracts were retrieved using a predicate-based (new) and keyword-based (baseline) approach. Each abstract was evaluated, double-blind, by cancer researchers on a 0-5 point scale to calculate precision (0 versus higher) and relevance (0-5 score). Precision was significantly higher (p<.001) for the predicate-based (80%) than for the keyword-based (71%) approach. Relevance was almost doubled with the predicate-based approach-2.1 versus 1.6 without rank order adjustment (p<.001) and 1.34 versus 0.98 with rank order adjustment (p<.001) for predicate--versus keyword-based approach respectively. Predicates can support more precise searching than keywords, laying the foundation for rich and sophisticated information search.

The significance of p53 isoform expression in serous ovarian cancer.

Epithelial ovarian cancer still carries a high mortality rate and remains the leading cause of gynecologic cancer death in the USA, despite decades of research. Hence, there is considerable interest in developing biomarkers that could be used to stratify patients for subsequent treatment. Mutation of the p53 tumor suppressor gene occurs very frequently (∼96%) in high-grade serous ovarian cancer. However, loss of p53 has not proven to be a reliable prognostic marker. Recent evidence indicates that the truncated p53 protein isoforms can regulate activated p53 and thus may play a role in tumorigenesis. In the article by Hofstetter et al., the authors examined the relationship between the expression of two p53 isoforms (Δ133p53 and Δ40p53) and prognosis in patients with serous ovarian cancer. Their findings indicate that Δ133p53 constitutes an independent prognostic marker for improved recurrence-free and overall survival. Intriguingly, this relationship was observed in patients whose tumors expressed a mutant p53, suggesting that Δ133p53 might suppress the actions of mutant p53. The mutational status of p53 alone did not have prognostic significance. These studies suggest that mutant p53 activity may be counteracted by Δ133p53, which leads to a more favorable prognosis in advanced serous ovarian carcinomas. Novel therapeutic approaches could be built upon these findings.

Hypomethylation of the 14-3-3σ promoter leads to increased expression in non-small cell lung cancer.

The 14-3-3 proteins are a set of seven highly conserved proteins that have recently been implicated in having a role in human tumorigenesis. However, the mechanism by which 14-3-3 proteins may act in this capacity is not well understood. In this study, we examined the expression of one of the 14-3-3 family members, 14-3-3σ, since it was shown previously to be aberrantly altered in human tumors. Using quantitative rtPCR and immunohistochemistry, we found that the expression levels of 14-3-3σ were elevated in the majority of human non-small cell lung cancers (NSCLC) we examined. Surprisingly, we found that the 14-3-3σ gene was hypomethylated in lung tumors relative to normal lung tissue suggesting that decreased DNA methylation resulted in increased expression of 14-3-3σ in NSCLC. We also determined the gene copy number for 14-3-3σ in tumor samples and found no significant correlation with elevated mRNA expression. And also no mutations were found in 14-3-3σ gene. Overall, our data suggest that misregulated expression of 14-3-3σ gene may be due to altered methylation status. © 2011 Wiley-Liss, Inc.

Families Playing Animal Crossing Together: Coping With Video Games During the COVID-19 Pandemic.

The COVID-19 pandemic was stressful for everyone, particularly for families who had to supervise and support children, facilitate remote schooling, and manage work and home life. We consider how families coped with pandemic-related stress using the video game Animal Crossing: New Horizons. Combining a family coping framework with theorizing about media as a coping tool, this interview study of 27 families (33 parents and 37 children) found that parents and children individual coped with pandemic-related stress with media. Parents engaged in protective buffering of their children with media, taking on individual responsibility to cope with a collective problem. Families engaged in communal coping, whereby media helped the family cope with a collective problem, taking on shared ownership and responsibility. We provide evidence for video games as coping tools, but with the novel consideration of family coping with media.

P53 is transported into the nucleus via an Hsf1-dependent nuclear localization mechanism.

Loss of p53 function can occur through disruption of its ability to localize to the nucleus. Previously we showed through characterization a set of mutant cell lines that lacked the ability to import p53 into the nucleus that nuclear translocation of p53 appeared to be mechanistically different from that of the SV40 T-antigen (SV40TAg). Here we extend that work by examining nuclear importation of p53 and SV40TAg using both in vivo and in vitro assays for nuclear localization. We show that disruption of microtubule polymerization using colchicine suppresses nuclear localization of p53 but not of SV40TAg. We also show, for the first time, that the heat shock transcription factor (Hsf1), is required for establishment of the microtubule network in cells and for nuclear localization of p53. In contrast, SV40TAg does not interact with polymerized microtubules suggesting that it is transported into the nucleus through an alternative mechanism. Interestingly, lacking of Hsf1 expression and suppressing Hsf1 by siRNA also made cells more resistant to the cytotoxic effects of paclitaxel. Hence, loss of Hsf1 activity not only suppressed p53 function, but also led to reduced sensitivity to killing by drugs that target microtubules.

P53 suppresses expression of the 14-3-3 gamma oncogene.

BACKGROUND: 14-3-3 proteins are a family of highly conserved proteins that are involved in a wide range of cellular processes. Recent evidence indicates that some of these proteins have oncogenic activity and that they may promote tumorigenesis. We previously showed that one of the 14-3-3 family members, 14-3-3 gamma, is over expressed in human lung cancers and that it can induce transformation of rodent cells in vitro. METHODS: qRTPCR and Western blot analysis were performed to examine 14-3-3 gamma expression in non-small cell lung cancers (NSCLC). Gene copy number was analyzed by qPCR. P53 mutations were detected by direct sequencing and also by western blot. CHIP and yeast one hybrid assays were used to detect p53 binding to 14-3-3 gamma promoter. RESULTS: Quantitative rtPCR results showed that the expression level of 14-3-3 gamma was elevated in the majority of NSCLC that we examined which was also consistent with protein expression. Further analysis of the expression pattern of 14-3-3 gamma in lung tumors showed a correlation with p53 mutations suggesting that p53 might suppress 14-3-3 gamma expression. Analysis of the gamma promoter sequence revealed the presence of a p53 consensus binding motif and in vitro assays demonstrated that wild-type p53 bound to this motif when activated by ionizing radiation. Deletion of the p53 binding motif eliminated p53's ability to suppress 14-3-3 gamma expression. CONCLUSION: Increased expression of 14-3-3 gamma in lung cancer coincides with loss of functional p53. Hence, we propose that 14-3-3 gamma's oncogenic activities cooperate with loss of p53 to promote lung tumorigenesis.