bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3059: The Tmeff2 protein functions as a tumor suppressor and interacts with Sarcosine dehydrogenase
Authors: Overcash Ryan , Chen Xiaofei , Harris Mitchel , Hoffman Donald , Ruiz-Echevarria Maria J. 
Published: February 2011

Abstract
Tmeff2 is a gene with an expression profile limited to the brain and the prostate but shown to be frequently upregulated in prostate cancer. It encodes a type I transmembrane protein with a short cytoplasmic tail containing a potential G-protein activation domain and an extracellular domain containing two follistatin (FS) modules and an epidermal growth factor-like (EGF) domain. Although these features are suggestive of a function in signal transduction, the role of the Tmeff2 in prostate cancer, or the mechanism(s) that lead to its overexpression during the disease are unclear. In the present study, we evaluated the functional role of Tmeff2 in prostate tumorigenesis.
To investigate the function of the gene, Tmeff2 was overexpressed in TRAMP C1 murine prostate cancer cells and HEK293T cells, and the effects of overexpression on cellular growth and tumorigenicity were assessed. Tmeff2 overexpression in HEK293T cells almost completely abolished the ability of these cells to form colonies in soft agar and resulted in a 20-30% reduction in proliferation rates in these and TRAMP C1 cells, indicating that the gene may function as a tumor suppressor in prostate cancer cells. Moreover, although TMEFF2 overexpression alone did not induce apoptosis, it sensitized these cell lines to staurosporine or rapamycin-induced apoptosis, causing nearly a three-fold increase in the percentage of apoptotic cells.
In order to assess the molecular mechanism(s) by which Tmeff2 may suppress cellular growth and tumorigenicity, we screened Tmeff2 affinity complexes by mass spectrometry to search for candidate functional partner(s) of Tmeff2. Our results showed an interaction with Sarcosine Dehydrogenase (SARDH) an enzyme involved in the metabolism of sarcosine. This interaction was further confirmed by co-immunoprecipitation analysis. Importantly, sarcosine has recently been described as a biomarker for prostate cancer as it was shown to be highly increased in prostate and metastatic prostate cancer. In addition, it may also play a role in the biology of the cancer since it promotes cell invasion when added to benign prostate epithelial cells.
In summary, the results presented here suggest that Tmeff2 functions as a tumor suppressor for prostate cancer. Its interaction with SARDH may represent a mechanism by which Tmeff2 modulates tumorigenicity by altering the levels of sarcosine. Further analyses are necessary to determine the value of Tmeff2 as a prognostic marker.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3059.
Abstract 3067: Differential proteomic profilingidentifies HNSCCinvasion genes: GANAB is negative regulator in HNSCC invasion
Authors: Chiu Ching-Chi , Li Hsiao-Fang , Chen Yin-Ju , Chen Ann-Joy 
Published: February 2011

Abstract
Head and neck squamous cell carcinoma (HNSCC) is one of the most frequent cancer worldwide, however, highly invasive or metastatic characteristics are the common cause of treatment failure. In order to investigate the invasive mechanism of cancer, we established highly invasive sublines of five HNC cell lines by using Matrigel and Transwell selection method. After confirmed the invasion phenotype, the differential proteomes were determined using proteomic methods. Total of 420 protein bands were identified by mass spectrometry analysis, which corresponds to 184 proteins. There were 52 proteins identified more than twice of the four independent experiments, indicating the significance of these proteins in regulation of invasion phenotype. In which, 18 (35%) functions as cytoskeleton or adhesion molecules, 10 (19%) function as molecular chaperone, 9 (17%) belongs to metabolic enzymes, 8 (15%) involve in transcriptional or translational regulation, 7 (13%) involve in cellular signalling pathway. RT-PCR analysis revealed 13 genes that were consistently differentially expressed in the HNSCC invasion sublines. One of the most significantly change genes is GANAB. The treatment of GANAB-shRNA also resulted in augment of cell growth in all HNSCC cell lines, with approximately increase to 1.34 fold at day 5 (p &lt; 0.05). GANAB-shRNA transfected cells migrated 1.78 fold faster than control cells in in vitro wound healing assay. The GANAB silencing cell increase to 12.33 fold (p=0.005) in HNSCC cell lines. These results suggest that plays an important role in negative regulation of cell growth, migration and invasion. Using a cut-off value of a 1.5-fold differential expression in tumor verse normal tissues, 14 (44%) patients were found under-expressed in GANAB proteins. These results support our cellular findings and indicate that HNSCC.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3067.
Abstract 3071: Frequent silencing of protocadherin 17, a candidate tumour suppressor for esophageal squamous-cell carcinoma
Authors: Imoto Issei , Haruki Shigeo , Kozaki Ken-ich , Matsui Takeshi , Kawachi Hiroshi , Komatsu Shuhei , Muramatsu Tomoki , Shimada Yutaka , Kawano Tatsuyuki , Inazawa Johji 
Published: February 2011

Abstract
Protocadherins are a subfamily of the cadherin superfamily, but little is known about their functions. We identified a homozygous loss of protocadherin 17 (PCDH17) in the course of a program to screen a panel of esophageal squamous-cell carcinoma (ESCC) cell lines for genomic copy-number aberrations. PCDH17 mRNA was expressed in normal esophageal tissue but not in the majority of ESCC cell lines without a homozygous deletion of this gene, and restored in gene-silenced ESCC cells after treatment with 5-aza-2′-deoxycytidine. The DNA methylation status of the PCDH17 CpG-island correlated inversely with the PCDH17 expression, and a putative methylation-target region showed promoter activity. The methylation of the PCDH17 promoter was also associated with the silencing of gene expression in primary ESCC at least partly. Among primary ESCC cases, the silencing of PCDH17 protein expression was associated with a poorer differentiation status of ESCC cells, and possibly with prognosis in a subset of this tumour. Restoration of PCDH17 expression in ESCC cells reduced cell proliferation and migration/invasion. These results suggest that silencing of PCDH17 expression through hypermethylation of the promoter or other mechanisms leads to loss of its tumour-suppressive activity, which may be a factor in the carcinogenesis of at least some ESCCs.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3071.
Abstract 3084: Chfr in breast cancer development
Authors: Jha Saheli , Banerjee Snigdha , Mehta Smita , Kambhampati Suman , Haque Inamul , Banerjee Sushanta K. 
Published: February 2011

Abstract
Breast cancer is a common malignancy and is the most frequently diagnosed cancer in USA. It can be developed when genes that control the cell cycle and genomic stability are aberrantly expressed or non-functional. Where CHFR encodes an ubiquitin ligase that reportedly delays mitosis in response to microtubule-targeting drugs (i.e. nocodazoles and taxanes). CHFR (Checkpoint with FHA and Ring Finger) is hypothesized to mediate a delay in cell cycle progression, early in mitosis, in response to microtubule stress, independent of the spindle assembly checkpoint. As a potential regulator of cell cycle progression, CHFR naturally becomes an interesting target for understanding cancer cells. Low or moderate CHFR mRNA expression has been already reported in many cancers including breast cancer with some relevance to tumor suppressor activities. In this study we analyzed the expression profiles of CHFR in different breast cancer cell lines at mRNA and protein levels using real-time PCR and immuno-Western blot analysis. We also analyzed its expression in various breast tissue samples using immunohistochemistry. We found CHFR mRNA was significantly higher in BT474 and MCF-7 cells as compared to MDA-MB-231 cells. Two isoforms (i.e.,) of CHFR protein were detected in these cells. High molecular weight (∼89kD) isoform was markedly elevated in MDA-MB-231 cells as compared to MCF-7 cells while low molecular weight (∼52kD) isoform markedly reduced in MDA-MB-231 cells. Moreover, in normal breast sample CHFR expression is nuclear while in adenocarcinoma samples CHFR was prominent expression in cytoplasmic. Finally, we found that high molecular weight CHFR isoform expression can be regulated negatively by CCN5/WISP-2, an anti-invasive gene. Collectively, these studies suggest that CHFR may play dual roles in the genesis of breast cancer and possibly, the high molecular weight isoform may play critical role in progression of breast cancer.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3084.
Abstract 3096: c-Myc regulates MAP4K1 expression and AP-1 activity in Pdcd4 knock-down cells
Authors: Yang Hsin-Sheng , Wang Qing 
Published: February 2011

Abstract
Programmed Cell Death 4 (Pdcd4) is a novel tumor suppressor that frequently exhibits down-regulated expression in several types of cancer. In colon cancer tissues, expression level of Pdcd4 is continuously down-regulated in the order of normal-adenoma-carcinoma. Over-expression of Pdcd4 has been demonstrated to inhibit 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced transformation and tumor phenotype. In addition to cultured cells, Pdcd4 transgenic mice that over-express Pdcd4 in the epidermis show significant reductions in 7,12-dimethylbenz(a)anthracene (DMBA)/TPA induced skin papilloma formation and carcinoma incidence. Knock-out of Pdcd4 expression in mice resulted in induction of lymphomas with frequent metastases to the liver and kidneys, and an increase in DMBA/TPA induced skin papilloma formation and carcinoma incidence. These findings suggest that Pdcd4 suppresses carcinogenesis not only at an early stage (tumor promotion), but also at a late stage (tumor progression) in both cultured cells and transgenic mice.
Recently, we demonstrated that over-expression of Pdcd4 inhibits invasion and MAP4K1 expression in colon tumor cells. Conversely, knock-down of Pdcd4 promotes invasion, activates AP-1 and β-catenin/Tcf dependent transcription, and up-regulates c-Myc expression in colon tumor cells. However, how MAP4K1 expression is regulated by Pdcd4 remains unknown. MAP4K1, a kinase upstream of JNK signaling pathway, is also known as HPK1 (haematopoietic progenitor kinase 1) whose function and expression regulation in solid tumors is not well studied. It has been known that activation of MAP4K1 results in activation of JNK, c-Jun and AP-1 dependent transcription. In the present study, we found that MAP4K1 expression is up-regulated by Pdcd4 knock-down. Concurrently, the phosphorylation of JNK and c-Jun is increased in Pdcd4 knock-down cells. c-Myc is a direct downstream target gene of β-catenin/Tcf dependent transcription and is up-regulated by Pdcd4 knock-down. To investigate the role of c-Myc in regulating MAP4K1 expression, we over-expressed c-Myc in HEK293 cells and found that over-expression of c-Myc induces MAP4K1 expression and activates c-Jun. Using chromatin immunoprecipitation, we demonstrate that c-Myc directly binds to MAP4K1 promoter in Pdcd4 knock-down cells. Down-regulation of c-Myc using c-myc RNAi reverses MAP4K1 expression and c-Jun activation in Pdcd4 knock-down cells. Thus, these results provide an insight into how Pdcd4 regulates MAP4K1 expression and AP-1 dependent transcription.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3096.
Abstract 3101: Pituitary homeobox 2 (PITX2) promotes thyroid carcinogenesis by activation of cyclin D2
Authors: Huang Yue , Zhu Guozhang 
Published: February 2011

Abstract
Pituitary homeobox 2 (PITX2), a Paired-like homeodomain transcription factor and a downstream effector of β-catenin signaling, plays substantial roles in normal embryonic development but its possible involvement in tumorigenesis was unknown. In this study, we extend its function in human cancer. Remarkably, we found that PITX2 was frequently overexpressed in human cancerous (papillary, follicular, and anaplastic) thyroid tissues, indicating for the first time that overactivated PITX2 may contribute to thyroid cancer. Cell-based and biochemical studies were performed to uncover the molecular mechanism of PITX2 action in thyroid cancer. Knockdown of PITX2 gene expression in human thyroid cancer cells significantly reduced cell proliferation and soft-agar colony formation. Biochemical analysis of cell cycle regulators upon PITX2 knockdown revealed down-regulation of all three D-type Cyclins (Cyclin D1, Cyclin D2 and Cyclin D3), dephosphorylation of Rb, and up-regulation of p15(INK4B) and p27(Kip1). Chromatin immunoprecipitation and promoter reporter assay indicated that Cyclin D2 was a direct target gene of PITX2. Consistently, we observed that high expression levels of Cyclin D2 were frequently associated with PITX2 overexpression in thyroid cancer tissues. To confirm our results in vivo, we took advantage of a mouse model of thyroid cancer (TRbetaPV/PV mouse). Consistently, the aberrant elevation of Pitx2 levels in the thyroid cancer of TRbetaPV/PV mice was accompanied by up-regulation of Cyclin Ds, increased phosphorylation of Rb, and down-regulation of p15(INK4B). Collectively, our findings demonstrate that the overactivated PITX2-Cyclin D2 pathway promotes thyroid tumorigenesis, and they provide the first evidence implicating an oncogenic role of PITX2 in human cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3101.
Abstract 3105: Expression of Wip1, a homeostatic regulator, is competitively controlled by c-Jun and p53 in response to UV irradiation
Authors: Song Ji-young , Park Ji-young , Kim Hyun-mi , Kim Jae-yong , Choi Jene 
Published: February 2011

Abstract
Wild-type p53-induced phosphatase (Wip1) is induced by p53 in response to various stresses, resulting in the dephosphorylation of proteins (i.e., p38 MAPK, p53, and uracil DNA glycosylase) involved in DNA repair and cell cycle checkpoint pathways. The p38 MAPK-p53 pathway has been a unique way for Wip1 induction as a stress responder. Here, we show that c-Jun directly binds to and activates the Wip1 promoter in response to UV irradiation. Mutation of the p53 response element (p53RE) or c-Jun consensus sites reduced promoter activities in both non-stressed and stressed A549 cells. Intriguingly, overexpression of p53 significantly decreased Wip1 expression in HCT116 p53+/+ cells but increased Wip1 expression in HCT116 p53−/− cells. Adenovirus-mediated p53 overexpression greatly decreased JNK activity. Up-regulation of Wip1 via the p38 MAPK-p53 and JNK-c-Jun pathways is specific, as demonstrated by our findings that p38 MAPK and JNK inhibitors affected the expression of Wip1 protein, whereas an ERK inhibitor did not. The JNK-c-Jun and p38 MAPK-p53 pathways were activated concomitantly in A549 cells; however, c-Jun activation occurred much more quickly, and to a greater extent, in A549-E6 cells, with delayed but fully induced Wip1 expression. Collectively, these data indicate that Wip1 is activated via both the JNK-c-Jun and p38 MAPK-p53 signaling pathways and that temporal induction of Wip1 largely depends on the balance between c-Jun and p53, because of their competition for JNK binding. Moreover, our results suggest that JNK-c-Jun-mediated Wip1 induction could serve as a major signaling pathway in human tumors, because of frequent p53 mutation.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3105.
Abstract 3127: Protein kinase D1 downregulation facilities PMA-induced apoptosis in LNCaP prostate cancer cells
Authors: Chen Jun , Giridhar Karthik V. , Wang Qiming Jane 
Published: February 2011

Abstract
Phorbol esters, analogs of diacylglycerol, induce apoptosis in androgen-sensitive LNCaP prostate cancer cells. Although the apoptotic pathways induced by PMA are well characterized, little is known of PMA-regulated pro-survival pathways such as ERK1/2 and Akt. We now provide experimental evidence to indicate that PKD1 promotes survival signals in LNCaP cells in response to PMA treatment. In turn, PMA induces dose- and time-dependent downregulation of PKD1 to facilitate apoptosis. This effect can be blocked by PKC inhibitor Ro 31-8220, indicating that PKC activation is required for PKD1 downregulation. Depletion of endogenous PKCδ and PKCε reveals that PKD1 activation and subsequent downregulation are mainly controlled by PKCδ. Knockdown of endogenous PKD1 and PKD2 decreases ERK1/2 and Akt activities and potentiates PMA-induced apoptosis as measured by cleaved PARP and sub-G0/G1 population, whereas overexpression of wild-type and constitutive-active PKD1 enhances ERK1/2 and Akt activities and suppresses PMA-induced apoptosis. Further analysis shows that the downregulation of PKD1 is mediated by ubiquitin/proteasome degradation pathway. In summary, our data indicate that PKD1 plays a pro-survival role in PMA-induced apoptosis by modulating downstream ERK1/2 and Akt activities.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3127.
Abstract 3134: Oncogenic functions of Secreted Frizzled-Related Protein 2 (sFRP2) in human renal cancer
Authors: Yamamura Soichiro , Kawakami Kazumori , Hirata Hiroshi , Ueno Koji , Saini Sharanjot , Majid Shahana , Carroll Peter , Dahiya Rajvir 
Published: February 2011

Abstract
The secreted Frizzled-related proteins (sFRPs) are modulators of the Wnt signaling pathway which is involved in embryonic development and tumor progression. The functions of secreted frizzled-related protein 2 (sFRP2) have not been studied in renal cancer. Human renal cancer tissue microarray revealed that the level of sFRP2 expression was high in normal kidney, low in primary renal cancer tissues and high in metastatic renal cancer tissues, suggesting different roles of the sFRP2 gene in different grades of renal cancer. To study the functions of sFRP2 gene in renal carcinoma cells, we established A498 renal cancer cell lines which stably expressed sFRP2. Stably expressed sFRP2 significantly promoted cell proliferation in vitro and in vivo tumor growth. The stably expressed sFRP2 cells were also found to reduce UV-induced apoptosis and increase in the G2 phase of the cell cycle. In the stable sFRP2 cell lines, expression of c-Fos, Bcl2, Bcl-w, cyclinB2 and cyclinE2 genes was significantly increased and p53 expression was decreased. In metastatic Caki1 cells, sFRP2 knockdown inhibited invasion and reduced expression of CD146, MMP2 and Rac1/2/3 genes. This is the first report documenting that sFRP2 modulates proliferation and invasion pathways by altering various genes in renal cancer cells. This data may provide better strategies for the management of renal cancer through regulation of sFRP2 pathways.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3134.
Abstract 3139: Chromosomal copy number alterations involved in Ras/PI3-kinase pathway in endometrial carcinomas
Authors: Ikeda Yuji , Oda Katsutoshi , Murayama-Hosokawa Satsuki , Nakagawa Shunsuke , Ishikawa Shumpei , Yamamoto Shogo , Shoji Keiko , Uehara Yuriko , Hiraike Osamu , Kawana Kei , Yano Tetsu , McCormick Frank , Kozuma Shiro , Taketani Yuji , Aburatani Hiroyuki 
Published: February 2011

Abstract
[Objectives]: Activation of Ras/PI3-kinase (PI3K) pathway plays a direct causal role in human cancer. Oncogenic mutant Ras remains in active state, and activates various Ras effectors, including PI3K pathway. Ras/PI3K pathway activating mutations are very frequent in endometrial cancer, as reported at 35-55% for PTEN, 25-36% for PIK3CA and 10-20% for K-Ras. NF1 is a negative regulator of Ras and its alterations have been reported in several types of tumors. Although LOH at PTEN locus (10q23.3) is reported at 15-30%, other chromosomal imbalances involved in the Ras/PI3K pathway are not well characterized in endometrial cancer. In this study, we focused on chromosomal copy number alterations (CNAs), including copy number neutral (CNN) LOH, involved in the Ras/PI3K pathway in endometrial carcinomas.
[Materials and Methods]: Under the approval of institutional ethical committees, we performed 250K or 50K Single Nucleotide Polymorphism (SNP) arrays in 31 endometrial carcinomas with paired DNA and examined allele-specific CNAs at K-Ras, NF1, PIK3CA and PTEN.
[Results]: We detected deletions of PTEN locus in eight out of 31 (26%) tumors; one with homozygous deletions (HD), four with CNN LOH and three with LOH without gain of the opposite allele. In addition to one HD (3%) and three LOH (10%) at NF1 locus, we found gains at the loci of PIK3CA (3q26.3) in four (13%) tumors and K-Ras (12p12.1) in four (13%) tumors. Taken together, we detected 12 (39%) tumors with one or more CNAs involved in the Ras/PI3K pathway. All the four tumors with NF1 deletions coexist with other CNAs involved in the Ras/PI3K pathway (Table). [Conclusion]: Our data unveiled CNN LOH of PTEN and homozygous deletions of PTEN and NF1, which had not been reported by conventional CGH analysis. Various types of CNAs might play roles in activation of the Ras/PI3K pathway and targeting the Ras-PI3K pathway might be effective in endometrial carcinomas with the Ras-PI3K related CNAs.Table.Coexistent CN alterations in the Ras/PI3K pathwayPTEN (Loss)PIK3CA (Gain)K-Ras (Gain)NF1 (Loss)LOH Gain LOH LOH Gain LOHLOHGain HDLOHGainGainLOH
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3139.