bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3270: Gene expression profiling of breast tumors from African American and Caucasian women: Are molecular differences meaningful
Authors: Valente Allyson L. , Shriver Craig D. , Ellsworth Rachel E. 
Published: May 2015

Abstract
Background: To identify molecular factors associated with survival disparities, multiple studies have identified differentially expressed genes in tumors from African American women (AAW) compared to Caucasian women (CW), however, it is not clear whether these changes, such as increased expression of PHSPL, SOS1 and CRYBB2P1 in tumors from AAW, are clinically meaningful or represent population artifact. Gene expression data were thus evaluated in breast tumors with defined intrinsic subtypes, non-malignant breast tissue and blood from patients without breast disease.
Methods: Gene expression data was generated using U133 2.0 microarrays for 184 breast tumors from AAW and CW matched by subtype, grade, age and presence of local or distant metastases, from 44 benign biopsy specimens, and from 143 peripheral blood samples from patients without current or past invasive breast disease. Principal component analysis (PCA) was performed using Partek Genomics Suite 6.6 and differentially expressed genes were detected using ANOVA with FDR&lt;0.05, 2-fold difference defining significance.
Results: When all tumors were analyzed together, only PSPHL, CRYBB2P1 and SOS1 were differentially expressed, each at significantly higher levels in tumors from AAW. When analyzed by subtype, PSPHL, CRYBB2P1, SOS1 and AMFR were expressed at higher levels in luminal A tumors (n=86) and SOS1 at higher levels in basal-like tumors (n=66) from AAW; no differentially expressed genes were detected in HER2-enriched (n=18) or luminal B (n=14) tumors. AMFR, CRYBB2P1, PSPHL and SOS1 were also expressed at significantly higher levels in both non-malignant breast tissue from AAW patients, and in blood specimens from disease-free AAW patients compared to non-malignant and blood specimens from CW.
Conclusions: PCA demonstrates that molecular profiles of tumors from AAW are highly similar to those from CW; the few genes that are differentially expressed in tumor specimens are not associated with breast cancer as the same changes are also found in disease-free breast tissues as well as blood from patients without breast disease. Lack of meaningful genetic differences, even within specific tumor subtypes, suggests that disparity differences between AAW and CW with breast cancer are not attributable to molecular differences inherent to the tumors, but likely stem from other factors such as genetic predisposition to the development of basal-like tumors or altered provision of or response to treatment.
Citation Format: Allyson L. Valente, Craig D. Shriver, Rachel E. Ellsworth. Gene expression profiling of breast tumors from African American and Caucasian women: Are molecular differences meaningful. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3270. doi:10.1158/1538-7445.AM2014-3270
Abstract 3289: Elevation of oxidative expression proteins in human ovarian epithelial carcinoma
Authors: Mehrabi Sharifeh , Cohen Shakeria , Aikhionbare Felix O. 
Published: May 2015

Abstract
Oxidative stress, which results from an imbalance between ROS and antioxidant capacities, can cause a wide range of direct or indirect DNA damage to ovarian epithelium mucosa that is exposed to immense physiological changes, driven by cyclically altering hormone levels as a result of ovulation. The influence of ovulation contributed to the cause of increased oxidative stress in ovarian cells. In this study, we monitored and compared the level of oxidized carbonyl proteins in two subtypes of epithelial ovarian cancer, Serous and endometriod with normal and normal surrounding tissue. We applied DNPH derivative colorimetric and immuneblot assay, two dimension gel electrophoresis (2-D SDS-PAGE), to identify and evaluate the level of oxidative modified protein in 100 snap-freeze epithelial ovarian tissues including, normal, normal surrounding, cystoadenoma, borderline and carcinoma with age range of 65±12, (56% Caucasian 44% Africa American. Our results showed that the index of carbonyl proteins /total proteins increased by onset and progression in both serous and endometriod ovarian malignancy. The elevation of oxidized proteins among African American was significantly higher than Caucasian in advanced stages of disease. SDS-PAGE profiles and western blot analysis of oxidized proteins showed a distinct protein expression pattern among cancerous and non-cancerous tissues. Our study suggests that the level of oxidative stress may be involved in the selective modification of some enzymes and structural proteins and could play a role in etiological differences that may exist between stages of benign and invasive epithelial ovarian tumors.
Citation Format: Sharifeh Mehrabi, Shakeria Cohen, Felix O. Aikhionbare. Elevation of oxidative expression proteins in human ovarian epithelial carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3289. doi:10.1158/1538-7445.AM2014-3289
Abstract 3291: Geranylgeranylation signals to the hippo pathway for breast cancer cell proliferation and migration
Authors: Mi Wenyi , Lin Qiong , Childress Chandra , Yang Wannian 
Published: May 2015

Abstract
Protein geranylgeranylation (GGylation) is an important biochemical process for cellular localization of many signaling molecules including Rho and Rab small GTPases and heterotrimeric GTPase gamma subunits. Previous studies have shown that GGylation is essential for cancer cell survival. However, the molecular mechanism mediating the cell survival effect remains elusive. Here we show that the hippo pathway is the downstream pathway of GGylation in breast cancer cells. Inhibition of GGylation enhanced phosphorylation of Mst1, Mst2 and Lats1 kinases, and eliminated LPA-induced activation of Yap and Taz and the hippo pathway-dependent transcription of Cyr61 and CTGF. We have demonstrated that the inhibitory effects of atorvastatin, an inhibitor of the biosynthesis of geranylgeranyl pyrophosphate (GGPP), and GGTI-298, an inhibitor of geranylgeranyltransferase I (GGTase I), on cell proliferation and migration are dependent on the hippo pathway in the breast cancer cells. In addition, knockdown of Yap and Taz produced the similar inhibitory effect on the cell proliferation and migration to that of atorvastatin and GGTI-298, suggesting the functional correlation between GGylation and the hippo signaling. Thus, our studies have demonstrated that the hippo pathway mediates the GGylation-dependent cancer cell survival and migration.
Citation Format: Wenyi Mi, Qiong Lin, Chandra Childress, Wannian Yang. Geranylgeranylation signals to the hippo pathway for breast cancer cell proliferation and migration. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3291. doi:10.1158/1538-7445.AM2014-3291
Abstract 3298: Identifying a function for DHHC20 in breast cancer
Authors: Runkle Kristin B. , Terkowski Samantha , Stypulkowski Ewa , Witze Eric 
Published: May 2015

Abstract
Triple negative breast cancer (TNBC) accounts for 15-20% of all cancers and is associated with a high propensity of metastasis, an increased risk of recurrence and a disproportionate number of deaths. Currently, therapeutic options are lacking in their ability to effectively treat TNBC; therefore, identification of novel, targetable signaling pathways is of great importance. Analysis of The Cancer Genome Atlas revealed that expression of the palmitoyl transferase DHHC20 is altered in breast cancer. DHHC20 is one of 23 protein palmitoyl transferases identified in mammalian cells, which catalyze the transfer of palmitate to cysteine residues of target proteins. Protein palmitoylation is critical in the trafficking, localization and function of various proteins and alterations in the expression and function of several DHHC palmitoyl transferases have been observed in cancer. Surprisingly, substrate specificity remains largely unknown and with the exception of a few palmitoylated proteins including Ras and the sex steroid receptors, the function of DHHC proteins in cancer has been largely unexplored. We utilized a TNBC cell culture model system to characterize the function of DHHC20 in breast cancer. Suppression of DHHC20 using short-hairpin RNA silencing resulted in several phenotypes consistent with a role for DHHC20 in tumor dormancy and progression. Specifically, knockdown of DHHC20 in MDA-MB231 cells increased the expression of CDK inhibitors p21 and p27, slowed cell division rates from every 24 hours to every 72 hours and increased the proportion of cells undergoing cellular senescence. Additionally, suppression of DHHC20 increased chemotaxis and enhanced mitogenic signaling through the Erk pathway under nutrient deprivation conditions. Finally, DHHC20 expression was dramatically reduced following 24hr of serum deprivation and loss of DHHC20 expression enhanced the survival of MDA-MB231 cells under low nutrient conditions. These findings suggest that DHHC20-mediated protein palmitoylation regulates important aspects of breast cancer progression including cell cycle control, mitogenic signaling responses and cell migration. The implication of these findings is that targeting the DHHC20 pathway may be of therapeutic interest for TNBC.
Citation Format: Kristin B. Runkle, Samantha Terkowski, Ewa Stypulkowski, Eric Witze. Identifying a function for DHHC20 in breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3298. doi:10.1158/1538-7445.AM2014-3298
Abstract 3303: Engineering of highly controlled in vitro co-culture model to study the mesenchymal stem cells mediated signaling in breast cancer cells
Authors: Daverey Amita , Drain Allison , Crone Karleen , Kidambi Srivatsan 
Published: May 2015

Abstract
Mesenchymal stem cells (MSCs) mediated signaling in breast cancer cells (BCCs) are critical for epithelial-mesenchymal transition (EMT) and metastasis. The mutual interactions between tumor cells and MSCs via direct contact or paracrine interaction through the recruitment of growth factors, cytokines and chemokines are thought to modulate tumor growth, invasion, metastasis and angiogenesis. Therefore, the cell-cell interactions that control the behaviour of cancer cells are targets with as much potential for the development of effective therapies as the tumor cells themselves. To this end, co-culture of BCCs with MSCs is critical to understand the role of MSCs on breast cancer progression. However, establishing co-culture of these cells with BCCs is challenging as the variation in culture condition can compromise the viability and functionality of co-cultured cells. In the present study, we have developed an in vitro co-culture method for controlling the interaction of BCCs with MSCs using biocompatible synthetic materials. We used cationic and anionic polymers to create stable and consistent surfaces. After that, these polymers were screened for the selective adhesion of cells, to create the patterned co-culture of BCCs and MSCs. Unlike other synthetic and natural polymers, one of the greatest advantages of screened polymers is that they are biologically inactive material for BCCs and MSCs cells, thus, do not alter the gene or protein expression profile of BCCs and MSCs. Therefore, the results obtained using this method provide true interaction of BCCs with MSCs in co-culture system without interference of interaction of cells with matrix. In addition, the in vitro co-culture model established in this study provides advantage on random co-culture by spatially organise cells in definite patterns, thereby, controlling the number and interaction of BCCs with MSCs. Also, provides an opportunity to study direct (through E-cadherin) and indirect (through cytokines) interaction in a single system which is important to study collective response of interaction BCCs and MSCs on breast cancer biology. After established co-culture model, we investigated MSCs mediated signaling in BCCs. qRT-PCR, western blotting and immunostaining data suggested that MSCs induce the expression of oncogene, increased proliferation of BCCs and up or downregulate the gene related to the drug resistance.
Citation Format: Amita Daverey, Allison Drain, Karleen Crone, Srivatsan Kidambi. Engineering of highly controlled in vitro co-culture model to study the mesenchymal stem cells mediated signaling in breast cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3303. doi:10.1158/1538-7445.AM2014-3303
Abstract 3304: 17β-hydroxysteroid dehydrogenase type 1 is under negative regulation from miR-210 and 518c in breast cancer
Authors: Hilborn Erik , Hung Alexander , Jansson Agneta Jansson 
Published: May 2015

Abstract
17β-hydroxysteroid dehydrogenase (HSD) type 1 is an important mediator of estrogen bioactivity in the breast tissue, both in healthy epithelium and during breast cancer. The primary role of 17β-HSD type 1 is in catalyzing the NADH dependent reduction of estrone to the more potent estradiol. The expression of 17β-HSD type 1 has been shown to predict tamoxifen treatment in breast cancer patients, but the regulatory mechanisms of 17HSD type 1 is not well known. In order to further elucidate the regulatory mechanisms it was decided to study microRNA in relation to this protein in breast cancer cell-lines. We studied the effect of microRNA mimics 210 and 518c after transient transfection upon the expression levels of 17β-HSD type 1 mRNA in breast cancer epithelial cell-lines MCF-7 and ZR75-1. The expression of 17β-HSD type 1 was measured by semi-quantitative RT-PCR. The endogenous expression of 17β-HSD type 1 in MCF-7 is low while ZR75-1 express moderate levels. We show that microRNA-210 down regulates 17β-HSD type 1 mRNA levels to 75% of untreated cells in MCF-7, and to 85% in ZR75-1. In addition, microRNA-518c was shown to down-regulate 17β-HSD type 1 to 90% compared to the endogenous expression. MicroRNA-210 is well known adverse indicator of breast cancer outcome, impacting cell cycle, mitochondrial oxidative metabolism, angiogenesis, DNA damage response, and cell survival, and has been shown to be up-regulated by hypoxia. It seems logical that while the cells recover from their excessive proliferating and the ensuing hypoxia, local 17β-HSD type 1 are down-regulated to slow down the rate of proliferation thus giving the cancer time to recover. Less is known about microRNA 518c in breast cancer, and this modulation of 17β-HSD type 1 levels is the first clear indicator of its role in breast cancer. These findings indicate that 17β-HSD type 1 is under microRNA control, and that this may be one important mechanism by which its expression levels are regulated in breast cancer.
Citation Format: Erik Hilborn, Alexander Hung, Agneta Jansson Jansson. 17β-hydroxysteroid dehydrogenase type 1 is under negative regulation from miR-210 and 518c in breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3304. doi:10.1158/1538-7445.AM2014-3304
Abstract 3305: Glucocorticoid differentially regulates gene expression in luminal and basal subtypes of breast cancer
Authors: Ling Jun , Lopez-Dee Zenaida , Khan Shagufta H. , Kumar Raj 
Published: May 2015

Abstract
Steroid hormone receptors (SHRs), such as estrogen- and progesterone- receptors, are well-validated drug targets and prognostic indicators for breast cancer (BC). When targeting SHRs for BC therapy, the major challenge is how to increase the selectivity of drugs against SHRs in specific cell/tissue. While estrogen- and progesterone- receptors are well studied in BC, glucocorticoid (GC) as a ubiquitous stress activated steroid hormone is less investigated. However, the elevated GC circadian dynamics is associated with poor prognosis, and GC receptor (GR) is highly expressed in metastatic BC. GCs are used successfully as an adjuvant therapy to induce apoptosis of leukemia and lymphoma. However, when applied to BC, the results are controversial with most GCs showing either pro-survival or no effects. To analyze the underlying mechanisms, gene expression profiling was performed in this study using qRT-PCR array that covers the genes as the drivers of BC. Our results showed that compared to MCF7 (luminal subtype) cells, MDA-MB-231(basal B subtype) cells are more responsive to Dexamethasone (Dex; a synthetic GC) treatment with the higher number of genes that were either up- or down-regulated. Shared by both MCF7 and MDA-MB-231 cells, the Dex-regulated genes are highly related to cell adhesion and epithelial-mesenchymal transition (EMT), followed by the genes involved in signal transduction, cell division and apoptosis, including SERPIN-E1, CDKN2A, c-Myc, THBS1, Snai2 and E-cadherin. However, the up- and down-regulation patterns are different between MDA-MB-231 and MCF7 cells. Using a real-time label-free cell assay, we identified that Dex promotes MDA-MB-231 cell adhesion and migration but only the spreading for MCF7 cells, suggesting that there are cell-specific effects of GC/GR in different subtypes of breast cancer.
Citation Format: Jun Ling, Zenaida Lopez-Dee, Shagufta H. Khan, Raj Kumar. Glucocorticoid differentially regulates gene expression in luminal and basal subtypes of breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3305. doi:10.1158/1538-7445.AM2014-3305
Abstract 3309: Castration-resistant prostate cancer (CRPC) growth is mediated through gamma-aminobutyric acid a receptor (GABAAR)
Authors: Wu Weijuan 
Published: May 2015

Abstract
The GABAergic signaling and growth factor pathways have been implicated in neuroendocrine differentiation and CRPC progression. We hypothesized that the GABAergic signaling and epidermal growth factor receptor (EGFR) pathway worked together to promote prostate cancer (PCa) progression. Using androgen receptor (AR)-negative PC-3 cells and AR-positive LNCaP cells derived from human PCa patients, we demonstrated that both cell lines responded to GABA(10-7M - 10-14M) and isoguvacine [a GABAAR antagonist] (10-7M - 10-11M) treatments over two days with elevated growth in a concentration-dependent manner (n=3 for each). Both GABA and isoguvacine also significantly (p&lt;0.05) stimulated expressions of EGFR ligands (EGF, HB-EGF, and TGF-α) (n=3 for each) in both PCa cell lines as determined by real-time quantitative PCR. Immunoblot analyses indicated significant (p&lt;0.05, n=3) elevation of phosphorylation levels of EGFR (Tyr1068) and downstream signal component Src (Tyr416) after GABA and isoguvacine treatments in both cell types with the same temporal changes as those observed with EGFR ligand expressions. Further involvement of GABAAR and EGFR signaling pathway in GABA and isoguvacine-stimulated PCa cell growth and signal transduction was studied using picrotoxin (a GABAAR antagonist) (10-6M ) and gefitinib (an EGFR inhibitor)( 10-6M). Both picrotoxin and gefitinib significantly (p&lt;0.05, n=3) suppressed the GABA and isoguvacine-stimulated cell growth, as well as EGFR (Tyr1068) and Src (Tyr416) phosphorylation. Immunohistochemical studies of GABAAR α1 and phospho-Src (Tyr416) demonstrated that the presence of these molecules was largely limited to prostate carcinomatous glands, but the levels were extremely low or absent in the normal prostate. In addition, GABAAR α1 and phosphor-Src (Tyr416) were co-localized within the cancerous prostate. Our results demonstrate for the first time, that the GABAergic signaling in CRPC cells is mediated through the EGFR pathway, suggesting that GABA may work as autocrine or paracine to promote PCa progression. The clinical implications of this pathway in CRPC may be of significance by therapeutically targeting the GABAAR pathway.
Citation Format: Weijuan Wu. Castration-resistant prostate cancer (CRPC) growth is mediated through gamma-aminobutyric acid a receptor (GABAAR). [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3309. doi:10.1158/1538-7445.AM2014-3309
Abstract 331: Targeting MCL1 in NPM1-mutant AML
Authors: Qutob Haitham , Abdul-Aziz Amina , Proudfoot Amy , Grundy Martin , Russell Nigel H. , Pallis Monica , Seedhouse Claire H. 
Published: May 2015

Abstract
MCL1 and BCL2 are pro-survival molecules which inhibit the apoptosis of AML cells treated with cytotoxic chemotherapy. The nuclear chaperone NPM1 is the most frequently mutated gene in AML. Using siRNA, we established that knockdown of NPM1 reduced expression of both MCL1 (P=0.034) and BCL2 (P=0.025) and increased p53 expression (P=0.03) in NPM1-mutant OCI-AML3 cells. These effects were not seen in cells expressing wildtype NPM1. The differentiating agent ATRA also reduced expression of both MCL1 (P=0.005) and BCL2 (P=0.0005). ATRA (3 days, 500 nM) reduced cell number by 50% in OCI-AML3 cells through growth inhibition, inducing features of differentiation and very little apoptosis. Whereas inhibition of BCL2 using up to 3 µM ABT199 did not augment ATRA-mediated cell reduction in OCI-AML3 cells, RNApolymerase II inhibitors, which preferentially target proteins with a short half-life such as MCL1, and which induce apoptosis, acted additively with ATRA to kill OCI-AML3 cells. Primary AML cells with mutant NPM1 (n=38) expressed higher levels of MCL1 but not of BCL2 than NPM1 wildtype samples (n=61). Primary AML cells frequently co-harbour mutant NPM1 and mutations of the receptor tyrosine kinase FLT3. As FLT3 mutation drives aberrant MCL1, we examined the effects of ATRA on MCL1 in NPM1 mutant samples with and without a FLT3 mutation. ATRA (3 days, 500 nM) induced the downregulation (&gt;20%) of MCL1 in 4/4 primary NPM1 mutant/FLT3 wildtype AML samples compared to 0/3 primary NPM1 mutant/FLT3 mutant AML samples. MCL1 was also downregulated by ATRA in 2/5 double wildtype samples. BCL2 was downregulated by ATRA in 1/4 primary NPMmutant/FLT3 wildtype AML samples, 2/3 primary NPM1 mutant/FLT3 mutant AML samples and 2/5 double wildtype samples. In conclusion, we show that MCL1 levels can be downregulated by mutant NPM1 inhibition and by ATRA in NPM1mutant/FLT3wildtype AML cells. RNA polymerase II inhibitors are clinically available and this work shows that ATRA can enhance their cytotoxic activity.
Citation Format: Haitham Qutob, Amina Abdul-Aziz, Amy Proudfoot, Martin Grundy, Nigel H. Russell, Monica Pallis, Claire H. Seedhouse. Targeting MCL1 in NPM1-mutant AML. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 331. doi:10.1158/1538-7445.AM2014-331