bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A16: Loss of Hugl1 induces an EGF-dependent cellular transdifferentiation
Authors: Greenwood Erin , Ebertz David , Fabiano Anthony , Schroeder Joyce A. 
Published: May 2016

Abstract
Maintenance of cell polarity and tissue architecture are essential in preventing neoplasia. Three different protein complexes control cellular polarity, including the Par3/aPKC/Par6 complex, the Crumbs/Pals/Patj complex and the Scribble/Dlg/Lgl complex. Of these, only the loss of Lgl promotes massive tissue growth and cellular migration in Drosophila as well as altered cellular polarity. Humans have two well-conserved homologs, Hugl1 and Hugl2. Expression of Hugl1 is downregulated, lost, or mutated in many cancers, including colorectal, endometrial, hepatocellular carcinoma, malignant melanomas, and breast cancer. We have previously examined the role of Hugl1 and Hugl2 in breast epithelial cells and found that Hugl1 loss results in a failure of growth control, gain of mesenchymal phenotypes, and a loss of both apicobasal and planar polarity. We have now determined that these phenotypes represent a fundamental change in cellular differentiation and that loss of Hugl1 results in cellular transdifferentiation. Loss of Hugl1 expression in breast epithelial cells results in the induction of a mixed-phenotype population (composed of CD44high/CD49flow and CD44low/CD49fhigh), whose growth and migration are driven by the Epidermal Growth Factor Receptor (EGFR). These populations exhibit increased anchorage-independent growth and form soft agar colonies in an EGF-dependent manner, and these behaviors are selectively enhanced in the CD44high/CD49flow population. Hugl1 loss results in the mislocalization of EGFR, resulting in TAZ and SLUG nuclear translocation. Together, these data indicate that when Hugl1 is lost in normal epithelial cells, polarity loss is accompanied by a transdifferentiation and increased anchorage-independent growth and migration.
Citation Format: Erin Greenwood, David Ebertz, Anthony Fabiano, Joyce A. Schroeder. Loss of Hugl1 induces an EGF-dependent cellular transdifferentiation. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research; Oct 17-20, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(2_Suppl):Abstract nr A16.
Abstract A41: Hormonal-receptor positive breast cancer: IL-6 augments invasion and lymph node metastasis via stimulating cathepsin B expression
Authors: Hassan Ahmed Osama , Ibrahim Sherif A. , El-Ghonaimy Eslam A. , Hassan Hebatallah , El-Mamlouk Tahani , El-Shinawi Mohamed , Mohamed Mona M. 
Published: May 2016

Abstract
Hormonal-receptor positive (HRP) breast cancer patients with positive metastatic axillary lymph nodes (LNs) are characterized by poor prognosis and increase the mortality rate. The mechanisms by which cancer cells invade lymph node have not been fully explored yet. Studies showed that the expression of interleukin-6 (IL-6) cytokine and the proteolytic enzyme cathepsin B (CTSB) are associated with breast cancer poor prognosis. In the present study, we tested the effect of different concentration of IL-6 on invasiveness capacity of HRP breast cancer cell lines MCF-7 cells using in vitro invasion chamber assay. Moreover, we investigated the impact of IL-6 on expression and activity of CTSB. Our findings indicates that IL-6 fosters invasion potential of MCF-7 cells in a dose-dependent manner. Furthermore, MCF-7 cells displayed increased CTSB expression and activity with acquisition of fibroblastic morphology upon IL-6 induction. To validate our results in vivo we assessed the level of expression of IL-6 and CTSB in the carcinoma tissues of positive and negative axillary metastatic lymph-nodes in HRP breast cancer patients., Western blot and immunohistochemistry showed that the expression of IL-6 and CTSB were higher in carcinoma tissues with positive lymph node compared to carcinoma tissues of patients with negative lymph node. Collectively, our findings suggest that IL-6 and CTSB may play a role in lymph node in HRP breast cancer patients. Targeting IL-6-CTSB axis may emerge as a therapeutic approach for hormonal-receptor positive with positive lymph node breast cancer patients.
Note: This abstract was not presented at the conference.
Citation Format: Ahmed Osama Hassan, Sherif A. Ibrahim, Eslam A. El-Ghonaimy, Hebatallah Hassan, Tahani El-Mamlouk, Mohamed El-Shinawi, Mona M. Mohamed. Hormonal-receptor positive breast cancer: IL-6 augments invasion and lymph node metastasis via stimulating cathepsin B expression. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research; Oct 17-20, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(2_Suppl):Abstract nr A41.
Abstract A45: Breast tumor metabolism
Authors: Possemato Richard 
Published: May 2016

Abstract
Proliferative cells have an increased need for macromolecular precursors required to sustain proliferation. Therefore, alteration of metabolic pathway flux and metabolite consumption is a hallmark of the transformed state. We have begun to investigate the specific metabolic pathway rewiring that occurs in the transformation of human breast cells, and the different metabolic phenotypes exhibited in breast cancers of specific molecular subtypes. These efforts have focused on the contribution of proper amino acid management in supporting breast tumor metabolism. For example, we have observed that ER-negative breast cancers exhibit activation of the serine biosynthetic pathway, controlled primarily by the expression of the enzyme PHGDH. ER-negative breast cancer cell lines with high PHGDH expression depend on its continued expression to maintain viability, and PHGDH expression permits cells to survive in the absence of extracellular serine. We have also identified the enzyme SHMT2, responsible for catabolizing serine for use in cellular methylation reactions, as an important determinant for cellular survival in low oxygen conditions. Finally, we have uncovered a key enzyme required to catabolize cysteine for the biosynthesis of iron-sulfur clusters, as being required for breast cancer cells to proliferate in high-oxygen environments, or under conditions of oxidative damage. We will discuss our development of mouse models to both investigate the contribution of these metabolic pathways to breast tumorigenesis and develop strategies to impact breast cancer growth and development.
This work is supported by a Susan G. Komen Career Catalyst grant.
Citation Format: Richard Possemato. Breast tumor metabolism. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research; Oct 17-20, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(2_Suppl):Abstract nr A45.
Abstract A48: Role of premature mRNA cleavage and alternative polyadenylation in driving breast cancer
Authors: Ni Thomas K. , Kuperwasser Charlotte 
Published: May 2016

Abstract
There is increasing appreciation that alterations to epigenetic mechanisms contribute directly to breast cancer development. In cancer cells, one such mechanism, called alternative polyadenylation (APA), has been observed to cause a general shortening of mRNA through the usage and premature cleavage of upstream poly(A) signals (PAS). However, while it is hypothesized that APA may be linked to cancer pathogenesis, specific examples of causality between APA and cancer development have remained elusive. We report the identification of a truncated tumor suppressor, MAGI3, at both the mRNA and protein levels from the MDA-MB-231 breast cancer cell line. Using 3' rapid amplification of cDNA ends (RACE), we have determined that the truncated transcript arises due to premature cleavage and APA at a cryptic intronic PAS. We have previously demonstrated genetically and biochemically that MAGI3 functions as a mammary tumor suppressor by antagonizing the oncoprotein and Hippo pathway effector, YAP, via a physical sequestration mechanism. Importantly, here we find that the truncated gene product encoded by this aberrant MAGI3 transcript acts as a dominant-negative protein, preventing MAGI3-YAP physical association and thereby causing YAP nuclear activation and malignant transformation of cells. Since “epi-mutations” such as these play an important role in breast cancer development, yet cannot be detected by microarray or genome sequencing methodologies, we are currently undertaking analysis of large-scale, breast cancer RNA-Seq data to identify tumors that express the truncated driver mRNA and to determine the frequency of APA products in breast cancer. Knowledge of the clinically relevant proteins produced by APA that are unique to cancer cells may lead to new therapeutic opportunities for breast cancer.
Citation Format: Thomas K. Ni, Charlotte Kuperwasser. Role of premature mRNA cleavage and alternative polyadenylation in driving breast cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research; Oct 17-20, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(2_Suppl):Abstract nr A48.
Abstract A52: The microRNA control of 17β-hydroxysteroid dehydrogenase type 1 and 2 in breast cancer
Authors: Hilborn Erik , Stal Olle , Jansson Agneta 
Published: May 2016

Abstract
Introduction: Breast cancer is primarily a steroid hormone dependent disease, and up to 80% of all breast cancers express the estrogen receptors. Regulation of steroid hormone activity in the breast tissue is mediated by the aromatase enzyme and by the 17β-hydroxysteroid dehydrogenase (17β-HSD) enzyme family. 17β-HSD1s primary role is in catalyzing the NADH dependent reduction of esterone to estradiol. 17β-HSD2 acts in opposition to 17β-HSD1 and mediates a NAD(H) dependent conversion of estradiol to esterone. The combination of these two enzymes has been shown to be a good indicator of tamoxifen treatment benefit, as tumors with a high 17βHSD1/17βHSD2 ratio have less benefit from tamoxifen treatment. Furthermore, patients with high 17βHSD1 mRNA expression were shown to have shorter overall disease free survival and increased risk of relapse. Despite this, next to nothing is known about the control of the expression 17βHSD1 and 17βHSD2 by microRNA in breast cancer.
Aim: To identify key microRNA responsible for the regulation of 17βHSD1 and 17βHSD2 in breast cancer.
Materials and methods: We screened for the effect of microRNA mimics by in vitro transient transfection of breast cancer epithelial cell-lines T47D, MCF-7 and ZR75-1 as well as the epithelial cell-line MCF10A.
Results: The endogenous expression of 17β-HSD type 1 in MCF-7 is low while ZR75-1 and MCF10A express moderate levels and T47D expresses high levels. Here we show that microRNA-210, 4508, 1304-3p, 6832-5p, 892a and 3674 down regulate 17β-HSD type 1 mRNA levels to 20-60% of control levels in MCF-7 and T47D. The same miRs had either a reduced effect, or no effect in ZR75-1 and MCF10A. Furthermore, we show that miR-17, 873-5p, 744-5p and 4794 result in a 2-5 fold increase in the expression of 17β-HSD type 1 ZR75-1, T47D and MCF7. This effect was reduced to 0.5 fold in MCF10A. The endogenous expression of 17β-HSD type 2 is low in MCF7, moderate in ZR75-1 and T47D and very high in MCF10A. We show that miRs 2045p, 211-5p, 5006-3p, 4251, 4745-5p, 302d-5p, 498, 1305 and 205-3p down regulates 17β-HSD type 2 expression to 10-60% of endogenous levels in ZR75-1 and MCF7, and to 30-70% of endogenous levels in MCF10A.
Conclusion: These findings are the first which start to map out the microRNA regulation of 17β-HSD type 1 and 2 in breast cancer, and this may be one important mechanism by which their expression levels are regulated in the pathogenesis of breast cancer.
Citation Format: Erik Hilborn, Olle Stal, Agneta Jansson. The microRNA control of 17β-hydroxysteroid dehydrogenase type 1 and 2 in breast cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research; Oct 17-20, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(2_Suppl):Abstract nr A52.
Abstract A53: An analysis of breast cancer incidence in young women: A single site study
Authors: Makharadze Tamta 
Published: May 2016

Abstract
Background: Breast Cancer cases in women are on the rise. It is estimated to raise breast cancer cases in young women. There are no screening guidelines for women younger than 45 years old. Breast cancer in this age group is associated with higher morbidity and mortality compared to older women, thus the impact of the disease is significant.
Methods: A retrospective chart review was conducted for women diagnosed and treated for breast cancer at clinic from 2012 to 2014. Patients were stratified by age, under 45 y.o and over 45 y.o., Subjects with different grade and disease subtypes(triple negative; ER/PR+/HER1-, ER/PR+/HER3+) were selected in those groups. Descriptive analysis was performed.
Results: 130 patients were reviewed from 2012 to 2014. The analysis demonstrated that of all reviewed samples, breast cancer was detected in 23% of patients younger than 45 y.o. Data analysis also showed that ER/PR-, HER2 1+ (triple negative) samples were detected in 26% of women under 45 y.o., which is 18% more than in women over 45 y. o. (26% vs. 7.6%). ER/PR+/HER2 1+ 13% vs. 20% (difference 7%), ER/PR+/HER3+ 39% vs. 2.5%, G3 - 47% vs. 37.5; G2 - 43% vs. 60% respectively.
Conclusions: This retrospective study indicates that breast cancer diagnosed in women younger than 45 y.o. is associated with an aggressive clinical and molecular subtype. Delay in diagnosis has been a concern among this age group given the lack of screening guidelines. In our country Georgia screening starts from 40 years. More awareness, screening programs and trainings to both practitioners and young women should be implemented.
Note: This abstract was not presented at the conference.
Citation Format: Tamta Makharadze. An analysis of breast cancer incidence in young women: A single site study. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research; Oct 17-20, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(2_Suppl):Abstract nr A53.
Abstract A57: Evaluation of the pathologic predictors of treatment response to neoadjuvant chemotherapy for invasive lobular breast cancer
Authors: Tsai Michaela L. , Finkelstein Marsha J. , Lillemoe Tamera J. , Susnik Barbara , Grimm Erin , Kang Sung-Hae , Kelly Caitlin , Swenson Karen K. 
Published: May 2016

Abstract
Introduction: Neoadjuvant chemotherapy (NAC) is becoming the standard of care for locally advanced breast cancer as a tool to objectively measure treatment response prior to surgery, and to downstage tumors to permit breast conserving surgery. Invasive lobular carcinoma (ILC) comprises approximately 10% of all invasive breast cancers, but is less likely than invasive ductal carcinoma to respond to NAC. The purpose of this study was to explore pathological and molecular predictors of response to NAC in patients with ILC.
Study Methods: Retrospective pathology review was conducted of all consecutive cases of non-metastatic ILC patients who had received NAC and subsequent surgery for ILC (n=32) within the Allina Health system. Pre-treatment tumor size, grade, stage, HER2 status, hormone receptor status, sub-type, Ki-67 index, and post-treatment Residual Cancer Burden (RCB) were determined by breast pathologists. Mann-Whitney U and Chi-square tests with exact methods were used to test for between group difference of responders (RCB 0-1) versus non-responders (RCB 2-3) to NAC on continuous and dichotomous variables. Multivariate logistic regression was conducted to determine significant predictors of response to NAC.
Findings: On univariate analysis, pleomorphic subtype (p=.004), Ki-67 (p=0.013), and HER2 status (p=.054) were significant predictors of response to NAC. On multivariate analysis, HER2 and Ki-67 provided the most efficient model for predicting response to NAC. This model correctly classified 81.3% of patients, 81.8% of RCB 0/1 and 80% of RCB 2/3. Pleomorphic subtype was highly correlated to KI-67.
Conclusions: Despite a limited sample size, this study shows that pathologic predictors (pleomorphic subtype, Ki-67, and HER2 status) are significant predictors of response to NAC, and may be useful in determining which ILC patients will benefit from NAC. This is an important finding because NAC for non-responders may delay the initiation of surgery and hormonal treatments for ILC.
Citation Format: Michaela L. Tsai, Marsha J. Finkelstein, Tamera J. Lillemoe, Barbara Susnik, Erin Grimm, Sung-Hae Kang, Caitlin Kelly, Karen K. Swenson. Evaluation of the pathologic predictors of treatment response to neoadjuvant chemotherapy for invasive lobular breast cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research; Oct 17-20, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(2_Suppl):Abstract nr A57.
Abstract A60: DOK1 gene may act as a tumor suppressor in breast cancer
Authors: Buyru Nur , Tuna Esin , Ozdemir Filiz , Bulut Pelin , Dalay Nejat 
Published: May 2016

Abstract
The DOK1 (Downstream of Tyrosine kinase 1) gene is a putative tumor suppressor gene located on human chromosome 2p13 which is frequently rearranged in leukaemia and other human tumours. The DOK1 protein is a member of the Dok protein family comprising seven members. It inhibits MAP kinase activity and displays anti-proliferative activities. The DOK1 gene may act as a tumor suppressor gene in ovarian cancer, Burkitt lymphoma, head and neck cancer (HNC), chronic lymphocytic leukaemia (CLL) and lung cancer by inhibiting cell proliferation. So far there is no study in the literature analyzing the relationship between the DOK1 gene and breast cancer. The aim of this study was to investigate the role of the DOK1 gene in breast cancer.
The tumors and adjacent normal tissues were collected from 50 patients who underwent surgery for breast cancer at the Bezmialem Vakif University Medical Faculty. For expression analysis, after isolation of RNA cDNA was been obtained. Gene expression levels in the tumors and adjacent normal tissues were determined by quantitative RT-PCR using the 2-ΔΔCT method. The results were normalized using the G6PD gene as reference. For mutation analysis, DNA was isolated and analyzed by cycle sequencing to detect mutations. The SPSS 21.0 software package was used for statistical analysis. P&lt;0.05 was considered significant.
When the DOK1 expression levels in the tumors and adjacent normal tissues were compared we observed that DOK1 expression was decreased in 31 (62%) patients and increased in 16 (32%) patients. The decrease of DOK1 expression was associated with age (p=0.031), menopausal status (p=0.017), histologic type, (p=0.015) and stage (p=0.017).
We identified 11 different alterations in the non-coding regions of the gene. One of these alterations was in the 5'-UTR and the remaining 10 were located in the introns 1 and 4. We did not observe any significant association between the mutations and expression level of the DOK1 gene. Our results, suggest that the DOK1 gene might act as a tumor suppressor in breast cancer.
Citation Format: Nur Buyru, Esin Tuna, Filiz Ozdemir, Pelin Bulut, Nejat Dalay. DOK1 gene may act as a tumor suppressor in breast cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research; Oct 17-20, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(2_Suppl):Abstract nr A60.
Abstract B22: PSMD2 is a molecular marker for a poor prognosis and determines cancer stem cells traits in breast cancer
Authors: Jung So-Youn , Jo Seolwha , Kang Eunji , Noh Dong-Young , Han Wonshik 
Published: May 2016

Abstract
The cancer stem cell (CSC) hypothesis postulates that tumors are maintained by a self-renewing CSCs that is also capable of differentiating into non-self -renewing cell populations that constitute the bulk tumor mass. These cells have stem cell characteristics and may play a role in tumorigenic growth, metastasis, and therapeutic resistance. Here we interrogated the oncogenic roles of PSMD2, a subunit of the 19S regulatory complex of proteasomes, as a constituent of a signature is a candidate oncogene in breast cancer. PSMD2 is required for breast CSCs proliferation both in vitro and in vivo, as shRNA-mediated PSMD2 silencing attenuated tumor growth. Further, PMSD2 is sufficient to induce stem cell characteristics, as forced PSMD2 expression facilitated mammosphere formation and increased the CD44+ breast CSC-like population. Mechanistically, the action of PSMD2 for induction of breast stemness is mediated by transcriptional regulation of the Notch signaling pathway and PSMD2 inhibition were associated with changes in epithelial-mesenchymal transition (EMT) phenotype. Knockdown of PSMD2 induced dramatic morphological changes, the typical spindle-like appearance cells was replaced with the round shape, like epithelial morphology. Moreover, treatment of TGF-β, the main inducer of EMT, lead to increased expression of PSMD2. PSMD2 silencing up-regulated E-cadherin and down-regulated expression of vimentin, N-cadherin and snail, mesenchymal markers. Clinically, PSMD2 expression was elevated in basal-like TNBC (triple negative breast cancer), correlated with poor prognosis, insilico analysis on a dataset comprising over 2413 microarrays of the web application bc-GenExMiner. Altogether, our findings suggest that PSMD2 may be a good molecular target candidate and PSMD2 inhibitor may kills breast CSCs and ameliorates poor prognosis of breast cancer.
Note: This abstract was not presented at the conference.
Citation Format: Kyung-Min Lee, So-Youn Jung, Seolwha Jo, Eunji Kang, Dong-Young Noh, Wonshik Han. PSMD2 is a molecular marker for a poor prognosis and determines cancer stem cells traits in breast cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research; Oct 17-20, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(2_Suppl):Abstract nr B22.