bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2028: HOX genes in oral cancer: Expression profile and functional characterization
Authors: Coletta Ricardo D. , Bitu Carolina C. , Pereira Manoela , Lopes Marcio A. , Graner Edgard 
Published: July 2012

Abstract
Homeobox genes, specifically the HOX family, play an important role in the development by controlling cellular proliferation, differentiation and apoptosis. In the present study it was investigated whether genes of the HOX family play a role in oral cancer. Our results demonstrated that the expression of HOXA4, A5, A7, A10, B7, C4, C5, C6, C8, C9, C10, C11, D9, D10, D11 and D13 was statistically higher in oral squamous cell carcinoma (OSCC) samples when compared with those from normal oral mucosa. We further demonstrated that HOXA1 and HOXB7 overexpression in HaCAT human epithelial cell line promotes proliferation, whereas downregulation of HOXB7 endogenous levels in human oral carcinoma cells (SCC9 cells) decreases it. In OSCCs, expression of HOXB7 and Ki67, a marker of proliferation, correlate strongly with each other (rs=0.79, p&lt;0.006). High immunohistochemical expression of HOXB7 was correlated with T stage (p=0.06), N stage (p=0.07), disease stage (p=0.09) and Ki67 expression (p=0.01), and patients with tumors showing high number of HOXB7-positive cells had shorter overall survival (p&lt;0.08) and shorter disease-free survival after treatment (p&lt;0.10) compared with patients with tumors exhibiting low amount of HOXB7-positive cells. No correlation between HOXA1 and clinicopathological parameters was observed. Our data suggest that HOXA1 and HOXB7 may contribute to oral carcinogenesis by increasing tumor cell proliferation, and imply that HOXB7 may be an important determinant of OSCC patient's prognosis. Thus, dysregulated expression of specific members of the HOX family of homeobox genes is related to the tumorigenesis of oral cancers.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2028. doi:10.1158/1538-7445.AM2011-2028
Abstract 2031: A functional nuclear epidermal growth factor receptor, Src and Stat3 heteromeric complex in pancreatic cancer cells
Authors: Paladino David , Jaganathan Soumya , Yue Peibin , Bogdanovic Jelena , Huo Qun , Turkson James 
Published: July 2012

Abstract
Pancreatic cancer is an extremely lethal malignancy whose prognosis has not improved appreciably in the last decade. The disease is usually diagnosed only after it has reached an advanced or metastatic state but even local, surgically resectable, tumors have a fairly poor prognosis. This is further complicated by the fact that little is known about the underlying mechanisms of pancreatic cancer, as evidenced by a lack of any efficacious targeted therapies. While hyperactive epidermal growth factor receptor (EGFR), Src tyrosine kinase and Signal Transducer and Activator of Transcription (Stat)3 have been detected in pancreatic cancer and implicated in the disease, the exact mechanisms by which they promote the disease phenotype are not well understood. We present evidence of a functional heteromeric complex of EGFR, c-Src and Stat3 that is detected at the plasma membrane and cytoplasm, and inside the nucleus of pancreatic cancer cells. The inhibition of c-Src, but not EGFR kinase, reduced the level of nuclear EGFR levels. Furthermore, the inhibition of Src or EGFR kinase alone decreased nuclear Stat3 levels, while the greatest decrease occurred upon the combined inhibition of EGFR and Src kinase activities. Significantly, evidence shows that the nuclear EGFR, Src and Stat3 complex functions as a transcriptional complex. Thus, the siRNA knockdown of EGFR or Src, or the pharmacological inhibition of aberrant Stat3 activity only moderately decreased c-Myc, iNOS, and VEGF expression. By contrast, the knockdown of EGFR or Src together with the inhibition of Stat3 activity strongly suppressed c-Myc expression in Panc-1 and Colo-357 cells. Chromatin immunoprecipitation (ChIP) studies further validated these findings and showed that the nuclear EGFR, Src, and Stat3 complex is bound to the c-Myc promoter. Taken together, these data identify a novel and functional heteromeric EGFR, Src, and Stat3 complex that promotes the induction of c-Myc in pancreatic cancer cells. Our study provides additional insight into the mechanisms by which hyperactive EGFR, Src and Stat3 pathway promotes the pancreatic cancer phenotype.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2031. doi:10.1158/1538-7445.AM2011-2031
Abstract 2049: Role of hypoxia-induced upregulation of caveolin-1 in hepatocellular carcinoma cell migration and invasion
Authors: Wong Sivia Yuen Sze , Tse Edith Yuk Ting , Yam Judy Wai Ping 
Published: July 2012

Abstract
Intratumoral hypoxia occurs when cells in the inner core of solid tumor mass become deprived of oxygen. It correlates with an increased risk to develop metastasis. However, the molecular basis about the adaptation and survival of tumor cells in hypoxic environment remains obscure. Our recent data revealed that Cav1, a component of focal adhesion, is dramatically increased in metastatic hepatocellular carcinoma (HCC) cell lines and tissues, suggesting a role of Cav1 in HCC metastasis. In this study, we further investigated the potential role of Cav1 in HCC metastasis under hypoxia. Our data revealed that Cav1 mRNA and protein expressions were enhanced in various HCC cells lines when placed in hypoxic chamber or treated with hypoxic mimetic drug. Such upregulation of Cav1 was abolished with the addition of HIF1α inhibitor or depletion of HIF1α by siRNA. This suggests that hypoxia-induced Cav1 expression is HIF1α-dependent. Our findings also showed that HCC cells possessed enhanced motility under hypoxia. However, knockdown of Cav1 in HCC cells attenuated the capacity of cells to migrate and invade. Collectively, our study suggests that the increased motility of HCC cells conferred by the hypoxia-induced Cav1 expression is an adaptive mechanism of cells to survive under hypoxic stress.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2049. doi:10.1158/1538-7445.AM2011-2049
Abstract 2051: Hypoxia-induced triple suicide gene TK/CD/UPRT expression enhances cytotoxicity to GCV and 5-FC and radiosensitization in human colorectal cancer cells
Authors: Hsiao Hung-Tsung , Xing Ligang , Deng Xuelong , Sun Xiaorong , He Fuqiu , Ling C. Clifton , Li Gloria C. 
Published: July 2012

Abstract
The hypoxic microenvironment, an important feature of human solid tumors but absent in normal tissues, may provide an opportunity for cancer-specific gene theapy. We constructed two vectors, both under the control of nine copies of hypoxia responsive element (HRE): (1) a herpes simplex virus type 1 thymidine kinase (TK) and enhanced green fluorescent protein (eGFP) fusion gene, and (2) a triple-fusion-gene, cytosine deaminase (CD), uracil phosphoribosyltransferase (UPRT) and monomeric DsRed (mDsRed). Human colorectal cancer cells (HCT8) were transfected with these plasmids, singly or in combination. Stable HCT8-HRE cells were established that contained and expressed the hypoxia-inducible vectors (i.e. HRE-TK/eGFP, HRE-CD/UPRT/mDsRed, or both HRE-TK/eGFP and HRE-CD/UPRT/mDsRed), as assessed by RT-PCR, Western blots and fluorescence microscopy analysis. In in vitro studies, we showed that hypoxia-induced TK/eGFP and CD/UPRT/mDsRed expression not only increased cytotoxicity to GCV and 5-FC, but also led to significant radiosensitization. In HCT8-HRE tumors transplanted in athymic mice, the distribution of TK/eGFP and CD/UPRT/mDsRed co-localized with that of the hypoxia marker pimonidazole. In addition, the administration of GCV and 5-FC in combination with local irradiation resulted in significant tumor regression, greater than that observed with drug or radiation treatment alone. Our data suggest that the hypoxia-inducible TK/GCV+CDUPRT/5-FC triple gene therapy has the ability to specifically target hypoxic cancer cells and significantly improve tumor control in combination with radiotherapy. This novel model is a valuable tool for studying tumor hypoxia and hypoxia-targeted radio-gene therapy.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2051. doi:10.1158/1538-7445.AM2011-2051
Abstract 2057: Hypoxia stimulates the epithelial-mesenchymal transition of gastric cancer cells via TGF-β/ TGF-β receptor signaling
Authors: Matsuoka Junko , Y Masakazu , Kashiwagi Shinichiro , Kato Yukihiro , Fuyuhiro Yuhiko , Kubo Naoshi , Tanaka Hiroaki , Muguruma Kazuya , Yamada Nobuya , Maeda Kiyoshi , Ohira Masaichi , Ishikawa Tetsuro , Hirakawa Kosei 
Published: July 2012

Abstract
Introduction: Epithelial mesenchymal transition (EMT) is a cellular process during which epithelial cells acquire mesenchymal properties while losing cell-cell interactions and apicobasal polarity. EMT is considered to be correlated with malignancy of cancer cells and to be responsible for cancer invasion and metastasis. Patients with gastric cancer show a poor prognosis because of frequent metastasis. We previously reported that hypoxia was associated with distant metastasis and poor prognosis in gastric cancer. Therefore, we investigated the effect of hypoxic condition on EMT of gastric cancer cells.
Materials and Methods:Three gastric cancer cell lines, OCUM-2MD3, OCUM-2M, and OCUM-12 derived from gastric cancer were used. Cells were cultured in normoxia (21% O2) or hypoxia (1% O2). EMT rate was evaluated as the percentage of spindle-shaped cells of total cells. The expression level of TGF-β and TGF-β receptor was evaluated by real time RT-PCR. Effect of TGF-β or TGF-βR inhibitor, SB431542, on the EMT was evaluated by cell morphology.
Results: Hypoxia stimulated EMT of OCUM-2MD3 and OCUM-12 cells, but not that of OCUM-2M cells. The level of TGF-β expression was increased significantly (p&lt;0.001) under hypoxia in comparison with normoxia in all of three cell lines. The level of TGF-β receptor expression was increased in OCUM-2MD3 and OCUM-12 cells, but not OCUM-2M cells. TGF-βR inhibitor, SB431542, significantly suppressed EMT of OCUM-2MD3 (p=0.03) and OCUM-12 (p&lt;0.01).
Conclusion: Hypoxia stimulates the EMT of gastric cancer cells via TGF-β/ TGF-β receptor signaling. TGF-β receptor inhibitor might be promising for the treatment of gastric cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2057. doi:10.1158/1538-7445.AM2011-2057
Abstract 2064: Regulation of the VHL tumor suppressor protein in hypoxia and through the cell cycle
Authors: Gnarra James R. , Brown Julie , Liu Weijun 
Published: July 2012

Abstract
The von Hippel-Lindau (VHL) gene is a classical tumor suppressor and is inactivated in patients with von Hippel-Lindau disease, as well as the majority of patients with sporadic clear cell renal carcinoma (RCC). The VHL protein (pVHL) is an E3 ubiquitin ligase with many functions, including regulating the hypoxia response as well as microtubule stability. While the involvement of pVHL in targeting of HIF alpha subunits for ubiquitin-mediated degradation is well documented, less is understood about regulation of pVHL itself. We determined pVHL levels under normoxic (room air, 21% oxygen) and hypoxic (1% oxygen) conditions and found that pVHL levels decreased in hypoxia. VHL protein half-life was similar in cells cultured in normoxia or hypoxia, suggesting that pVHL expression is regulated through a post-transcriptional mechanism. Down regulation of pVHL in hypoxia suggests a novel and complementary mechanism to account for stabilization of HIF alpha subunits. While pVHL-negative RCC cells progress through the cell cycle when cultured in hypoxia, isogenic pVHL-expressing RCC exhibited hypoxia-induced arrest in G1 phase of the cell cycle. We also determined pVHL levels during cell cycle progression and found that pVHL levels were decreased levels during mitosis and G1. The anaphase promoting complex/cyclosome (APC/C) is an E3 ubiquitin ligase that is active during late M phase and G1 through the association with the activators, Cdh1 and Cdc20. Cdh1 and Cdc20 bind to APC/C target proteins through recognition of Destruction box consensus sequences. Such sequences are found in pVHL, suggesting that pVHL may be a target for APC/C ubiquitylation. We found that pVHL physically bound to Cdh1, that Cdh1 knockdown was associated with increased pVHL levels, that Cdh1 overexpression was associated with decreased pVHL levels and increased polyubiquitylation pVHL, and that these activities were dependent on pVHL Destruction box sequences. Our results indicate that pVHL is a novel substrate of APC/C-Cdh1.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2064. doi:10.1158/1538-7445.AM2011-2064
Abstract 2087: Estrogen receptor beta sensitizes breast cancer cells to endoplasmic reticulum stress-regulated apoptosis
Authors: Rajapaksa Gayani K. , Nikolos Fotis , Thomas Christoforos G. , Gustafsson Jan-Ake 
Published: July 2012

Abstract
Estrogen receptor beta (ERβ) as estrogen-regulated transcription factor is involved in the development of the normal mammary gland and affects the progression and the anti-estrogen resistance of breast cancer. Recent data connect this resistance with the activation of survival mechanisms including the unfolded protein response (UPR). The UPR assists the cells to cope with the stress induced upon accumulation of unfolded proteins in the endoplasmic reticulum (ER) named ER stress. Although estrogen receptor alpha (ERα) has been shown to alter the resistance of breast cancer cells to anti-estrogens by modulating the levels of ER stress, the role of ERβ in the regulation of the UPR has not been elucidated. Here we show that ERβ decreases the resistance of breast cancer cells to chemically-induced ER stress by altering the inositol-requiring enzyme-1 (IRE-1) pathway of the UPR. In particular, we found that induction in the expression of ERβ enhances apoptosis and upregulates the ER stress-regulated pro-apoptotic CHOP/GADD153 in MDA-MB-231 breast cancer cells in response to treatment with the ER stressor thapsigargin. ERβ induces apoptosis under ER stress by inhibiting the unconventional mRNA splicing of X-box binding protein-1 (XBP-1), and thus, attenuating the upregulation of the active transcription factor which reduces the load of unfolded proteins in the ER. These results suggest ERβ as a potential modulator of the resistance of breast cancer cells to ER stressors through regulating the UPR.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2087. doi:10.1158/1538-7445.AM2011-2087
Abstract 2099: Tid1 regulates galectin-7 mediated tumorigenesis of oral squamous cell carcinoma
Authors: Wu Yi-Chen , Huang Lu-Ying , Lo Jeng-Fan 
Published: July 2012

Abstract
Background: We previously identified Tid1, a DnaJ cochaperon protein, functions as a tumour suppressor in oral squamous cell carcinoma (OSCC) tumourigenesis (J Pathol 2009;219:347-55). To further understand the molecular mechanisms mediated by Tid1 on oral tumorigenesis, we applied affinity chromatography and systemic proteomics analysis to identify galectin-7, which specifically interacted with Tid1. Others have shown that Galectin-7 plays a number of important roles in tumor development. However, the role of Galectin-7 in OSCC tumourigenesis remains unclear. Herein, we elucidated the mechanism mediated by Tid1 on regulating galectin-7 mediated cellular signaling and tumorigenesis in OSCC.
Methods: First, through HA-tag affinity chromatography and mass spectrometry we identified substrate proteins that specifically interact with Tid1. Secondly, co-immunoprecipitation analysis and confocal microscope was performed to confirm the protein-protein interaction between galectin-7 and Tid1. In vitro tumorigenic properties of OSCC overexpressing galectin-7 were determined. Subsequently, the tumorigenic properties of OSCC after co-overexpression of galectin-7 and Tid1 were investigated. Finally, immunoprecipitation analysis was performed to recognize the Tid1 induced deregulation of galectin-7 by enhancing ubiquitination.
Results: We found out that Tid1 interacted with galectin-7. Furthermore, overexpression galectin-7 expression resulted in up-regulation migration, invasion and soft agar colony formation abilities in OSCC. Importantly, co-overexpression of Tid1 decreased the galectin-7 expression and impaired galectin-7-mediated migration, invasion and soft agar colony formation ability of OSCC. Finally, we found galectin-7 ubiquitination as revealed by antiubiquitin immunoblot analysis in immunoprecipitates.
Conclusion: Our studies first pointed out that galectin-7 played pivotal roles in OSCC tumorigenesis. Notably, we identified galectin-7 that specifically interacted with Tid1. We hypothesized that Tid1/ Hsp70 may regulate galectin-7 stability by ubiquitinylation. The molecular mechanism by which Tid1 negatively modulates the galectin-7 warrants further investigation.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2099. doi:10.1158/1538-7445.AM2011-2099
Abstract 2101: PMEPA1 co-operates with the androgen responsive gene, NEDD4-1, to control the androgen receptor levels in human prostate cancer cells
Authors: Li Hua , Chijioke Juliet , Sharad Shashwat , Dobi Albert , Srivastava Shiv 
Published: July 2012

Abstract
Androgen receptor (AR) is a male hormone receptor and a nuclear transcriptional factor that plays central role in the differentiation and growth of the prostate gland and alterations of the AR network contribute to prostate tumorigenesis. The stability of the AR protein has been known to be regulated by the MDM2 E3 ubiquitin ligase. Recent investigations from our group suggest the role of PMEPA1-NEDD4-1 negative feedback loop in the regulation of AR protein levels in prostate cancer cells. In the PMEPA1-NEDD4-1 feedback loop, AR transcriptionally activates PMEPA1, which in turn provides a docking platform to recruit NEDD4-1 E3 ubiquitin ligase, to facilitate the proteasome dependent degradation of the AR. We hypothesize that decreased or absent PMPEA1 expression observed in more than 65% for prostate tumors may lead to the gain of AR functions which contribute to prostate tumorigenesis. Here we further investigate how PMEPA1 recruits NEDD4-1 to alter AR protein levels and AR signaling in prostate cancer cells.
Androgen receptor positive prostate cancer cells lines, LNCaP and VCaP, were treated with synthetic androgen R1881 for 24 hours. The androgen receptor, PMEPA1 and NEDD4-1 were knocked down with specific small interfering RNA (siRNA) molecules. Wild-type AR and mt AR (T877A) were ectopically expressed in LNCaP cells with adenoviral expression vectors. Protein levels of AR, PMEPA1, NEDD4-1, as well as AR responsive gene PSA were assessed by immunoblot assays.
Our new observations revealed that that NEDD4-1 was androgen inducible in both LNCaP and VCaP cells. Over-expression of wild-type and mutant AR (T877A) resulted in the upregulation of NEDD4-1 in LNCaP cells. Consistent with these findings, inhibition of AR by siRNA lead to down-regulation of NEDD4-1. As expected, loss of PMEPA1 in LNCaP cells induced up-regulation of AR and NEDD4-1 in an androgen dose-dependent manner. Knockdown of NEDD4-1, rather than NEDD4-2, resulted in elevation of androgen receptor levels and decreases of PMEPA1 expression in LNCaP cells.
Our data suggest that NEDD4-1 is an androgen inducible gene and a complex inter-relationship between PMEPA1, NEDD4-1 and AR. Intriguingly, the AR degradation function of NEDD4-1 depends on the availability of PMEPA1. Thus PMEPA1-NEDD4-1 co-operation is critical for the regulation of androgen receptor protein levels. In conclusion, loss of PMEPA1 in human prostate cancer may also lead to the activation of NEDD4-1 through elevated AR signaling, representing a feed-forward event in tumorigenesis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2101. doi:10.1158/1538-7445.AM2011-2101