Oncology Research 19(1-2) Abstracts

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Volume 19, Number 2

Oncology Research, Vol. 19, pp. 55–66, 2010
0965-0407/10 $90.00 + .00
DOI: 10.3727/096504010X12864748215124
E-ISSN 1555-3906
Copyright © 2010 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Review

Cancer: A Novel “No-Nonsense” Approach to Treatment

John A. Loudon

Perfect Dental, Liverpool, Sydney, Australia

Nonsense mutations, which lead to premature termination codons, are prevalent in a wide variety of cancers and many studies highlight clear evidence of functions. Based on these observations, a strategy is proposed for using various natural and synthetic derivatives based on aminoglycosides and their conjugates that have the unique property of read-through of nonsense mutations. The results and current status of this group of drugs are presented to show their effectiveness in treating other nonsense-codon-mediated diseases unrelated to cancer such as cystic fibrosis, thalassaemia, and muscular dystrophy. Concluding remarks indicate that this novel approach to cancer treatment with relatively low toxicity and reversibility of drug action as well as potential good patient acceptance and compliance ought to be now trialed for use in treating a wide variety of cancers.

Key words: Aminoglycosides; Ataluren; Nonsense mutations; Ribosomal read-through; Tumor suppressor proteins

Address correspondence to John A. Loudon, Ph.D., BDS(hons), BSc(Dent)hons Syd, Cert Oral Path., FAAOMP, OH, Perfect Dental, Suite 3/158 Macquarie Street, Liverpool, Sydney, NSW, 2170, Australia. Tel: 61-2-9822-5590; Fax: 61-2-9822-5591; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 19, pp. 67–76, 2010
0965-0407/10 $90.00 + .00
DOI: 10.3727/096504010X12864748215043
E-ISSN 1555-3906
Copyright © 2010 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Hepatoma-Derived Growth Factor Regulates the Bad-Mediated Apoptotic Pathway and Induction of Vascular Endothelial Growth Factor in Stomach Cancer Cells

Kyung Hee Lee,* Eun Young Choi,* Min Kyoung Kim,* Si Hyung Lee,† Byung Ik Jang,† Tae Nyeun Kim,† Se Won Kim,‡ Sang Woon Kim,‡ Sun Kyo Song,‡ Jae-Ryong Kim,§¶ and Bo Chan Jung#

*Department of Hematology-Oncology, College of Medicine, Yeungnam University, Daegu, Korea
†Department of Gastro-Enterology, College of Medicine, Yeungnam University, Daegu, Korea
‡Department of Surgery, College of Medicine, Yeungnam University, Daegu, Korea
§Department of Biochemistry and Molecular Biology, College of Medicine, Yeungnam University, Daegu, Korea
¶Aging-Associated Vascular Disease Research Center, College of Medicine, Yeungnam University, Daegu, Korea
#Department of Laboratory Medicine, CHA Gumi Medical Center, Korea

Hepatoma-derived growth factor (HDGF) is highly expressed in tumor cells and may play an important role in the development and progression of carcinomas. However, the molecular mechanism by which HDGF participates in gastric carcinomatosis requires further analysis. In this study, we determined the role of HDGF in tumorigenesis and elucidated the mechanisms of action. To determine aggressive biological behavior, we knocked down HDGF expression with HDGF-specific shRNA in two gastric cancer cell lines. First, using cDNA microarrary, we showed that hepatocyte growth factor (HGF) induced HDGF and confirmed this by Western blotting. HGF increased HDGF in a dose-dependent manner. We also determined whether HDGF induces angiogenic factor, and found the vascular endothelial growth factor (VEGF) was induced by HDGF. Downregulation of HDGF resulted in a decrement of VEGF. HDGF knock-down was found to induce the expression of the proapoptotic protein, Bad, and also inactivate ERK, which in turn led to dephosphorylation of Bad at ser112 and ser136, and induced apoptosis. Transfection with HDGF-siRNA resulted in a decrement of cell proliferation, as determined with a MMT assay. In an in vitro invasion assay, significantly fewer cells transfected with HDGF-siRNA than control cells were able to invade across a Matrigel membrane barrier. Our results suggest that HDGF is involved in cell growth, cell invasion, and apoptosis. These qualities may contribute to the HDGF-associated aggressive biological behavior of gastric cancer and thus serve as a potential target for cancer therapy.

Key words: Hepatoma-derived growth factor (HDGF); Bad; Vascular endothelial growth factor (VEGF); Hepatocyte growth factor (HGF); Metastasis

Address correspondence to Jae-Ryong Kim, M.D., Ph.D., Department of Biochemistry and Molecular Biology, College of Medicine, Yeungnam University, 317-1 Daemyung-Dong, Daegu 705-717, Republic of Korea. Tel: 82-53-620-4342; Fax: 82-53-654-6651; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 19, pp. 77–83, 2010
0965-0407/10 $90.00 + .00
DOI: 10.3727/096504010X12864748215089
E-ISSN 1555-3906
Copyright © 2010 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Downregulation of Protein Kinase Cα Was Involved in Selenite-Induced Apoptosis of NB4 Cells

Zhu-shi Li, Ke-jian Shi, Li-ying Guan, Qian Jiang, Yang Yang, and Cai-min Xu

National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China

We revealed in our previous research that sodium selenite induced obvious apoptosis of human leukemia NB4 cells, with reactive oxygen species (ROS), mitochondrial apoptosis pathway, and endoplasmic reticulum stress (ER stress) involved. In the present study, we revealed protein kinase Cα (PKCα) was dramatically downregulated in selenite-induced apoptosis, which was mediated by ROS. Besides, we confirmed PKCα played an antiapoptotic role through its effects on ERK1/2 and Akt, while its downregulation was attributed to caspase-3 and PP2Ac under the regulation of ROS. In summary, we speculated that in apoptosis of NB4 cells induced by selenite, PKCα functioned to counteract apoptosis, thus its downregulation seemed a mechanism aggravating apoptosis.

Key words: Apoptosis; Protein kinase Cα (PKCα); Reactive oxygen species (ROS); Sodium selenite

Address correspondence to Cai-min Xu, Professor, National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Peking Union Medical College and Chinese Academy of Medical Sciences, 5 Dong Dan San Tiao, Beijing 100005, China. Tel: +86 10 65296445; Fax: +86 10 65296445; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 19, pp. 85–92, 2010
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DOI: 10.3727/096504010X12875107808008
E-ISSN 1555-3906
Copyright © 2010 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Invadopodia Formation by Bladder Tumor Cells

Mihoko Sutoh,* Yasuhiro Hashimoto,† Takahiro Yoneyama,‡ Hayato Yamamoto,† Shingo Hatakeyama,‡ Takuya Koie,‡ Akiko Okamoto,† Kanemitsu Yamaya,* Hisao Saitoh,† Tomihisa Funyu,*† Toshiya Nakamura,§ Tatsusuke Sato,¶ Chikara Ohyama,‡ and Shigeru Tsuboi*‡

*Department of Biochemistry, Oyokyo Kidney Research Institute, Hirosaki, Aomori, Japan
†Department of Urology, Oyokyo Kidney Research Institute, Hirosaki, Aomori, Japan
‡Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
§Department of Biomedical Sciences, Hirosaki University Graduate School of Health Sciences, Hirosaki, Aomori, Japan
¶Department of Pathologic Analysis, Hirosaki University Graduate School of Health Sciences, Hirosaki, Aomori, Japan

A major cause of death in patients with bladder tumors is recurrence with metastasis. Bladder tumor metastasis is largely dependent upon the invasive capacity of tumor cells. Tumor cell invasion is mainly mediated by actin-rich protrusive membrane structures called invadopodia. The formation of invadopodia was observed in various types of invasive tumors such as breast cancer and melanomas. However, invadopodia formation so far has not been described in bladder tumor cells. We here report that human bladder tumor cells form functionally active invadopodia. By using a confocal laser scanning microscope, we demonstrated that invasive bladder tumor cell lines, YTS-1 and T24, with high Matrigel degradation activity form invadopodia but that noninvasive bladder tumor cell lines, RT4 and KK-47, form no detectable invadopodia. Invadopodia formed by YTS-1 cells had the ability to secrete matrix metalloproteases and degrade extracellular matrix to invade surrounding areas. Moreover, we observed that primary tumor cells obtained from patients with invasive bladder tumors also form invadopodia, validating the results from bladder tumor cell lines. Our results provide evidence that invasive human bladder tumor cells form invadopodia for tumor invasion.

Key words: Invadopodia; Bladder tumor; Tumor invasion

Address correspondence to Shigeru Tsuboi, Department of Biochemistry, Oyokyo Kidney Research Institute, Hirosaki, Aomori 036-8243, Japan. Tel: 81-172-87-1221; Fax: 81-172-87-1228; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it or Chikara Ohyama, Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8562, Japan. Tel: 81-172-39-5091; Fax: 81-172-39-5092; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 19, pp. 93–97, 2010
0965-0407/10 $90.00 + .00
DOI: 10.3727/096504010X12828372551786
E-ISSN 1555-3906
Copyright © 2010 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Tumor MET Expression May Not Predict the Risk of Venous Thromboembolism in Cancer Patients

Hamid Sayar,* Jeffrey T. Bunning,† Therese J. Bocklage,‡ Sang-Joon Lee,§ Edward Libby,¶ and Ian Rabinowitz¶

*Indiana University Simon Cancer Center, Indianapolis, IN, USA
†Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA
‡Department of Pathology, 1 University of New Mexico, Albuquerque, NM, USA
§Division of Epidemiology and Biostatistics, 1 University of New Mexico, Albuquerque, NM, USA
¶University of New Mexico Cancer Research and Treatment Center, 1 University of New Mexico, Albuquerque, NM, USA

Venous thromboembolism (VTE) occurs at an increased incidence in cancer patients. A cancer-related hypercoagulable state has been considered to play role in this phenomenon. Preclinical data suggest an association between tumor expression of MET proto-oncogene (MET) and a hypercoagulable state, resulting in VTE. We investigated this association in this retrospective study. Thirty-five cancer patients with documented VTE and no relevant predisposing factors were compared with 35 matched cancer patients without VTE who served as controls. Pathology specimens of all patients and controls were stained by immunohistochemistry (IHC) for MET protein. Intensity of reactivity to the MET antibody was read as 0 (negative), 1+ (equivocal), and 2+ (positive). The pathologists were blinded to the patient VTE status. The MET reactivity in tissue sections were compared between the two cohorts. No significant difference was observed between the two groups for MET expression. This study’s findings indicate no association between the reactivity for MET protein as measured through an immunohistochemical technique, and the incidence of VTE in cancer patients.

Key words: MET; Hepatocyte growth factor; Thrombosis; Thromboembolism

Address correspondence to Hamid Sayar, M.D., Indiana University Simon Cancer Center, 535 Barnhill Dr., Room 473, Indianapolis, IN 46202-5289, USA. Tel: (317) 948-6871; Fax: (317) 944-3684; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 19, pp. 99–104, 2010
0965-0407/10 $90.00 + .00
DOI: 10.3727/096504010X12864748215007
E-ISSN 1555-3906
Copyright © 2010 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Brief Communication

Mutations in the HD and PEST Domain of Notch-1 Receptor in T-Cell Acute Lymphoblastic Leukemia: Report of Novel Mutations From Indian Population

Aparna A. Bhanushali,* Suresh Babu,† Veera Raghavan Thangapandi,† Renjith Pillai,† Pratiksha Chheda,* and Bibhu R. Das*

*Research and Development, Super Religare Laboratories Ltd., Mumbai, India
†Trainees-Research and Development, Super Religare Laboratories Ltd., Mumbai, India

Notch-1 is a transmembrane receptor protein that directs T-cell differentiation. Gain-of-function mutations in Notch-1 have been reported in more than 50% of human T-cell acute lymphoblastic leukemia (T-ALL). The current study was undertaken to characterize mutations in the heterodimerization (HD) domain and proline, glutamic acid, serine, threonine-rich (PEST) domain of the Notch-1 receptor. RNA was isolated from peripheral blood/bone marrow of 15 de novo T-ALL subjects; the Notch-1 HD and PEST regions were amplified and sequenced. Overall six patients (40%) had at least one Notch-1 mutation, 2/15 (13%) in the HD and 4/15 (27%) in the PEST domain. None of the samples showed simultaneous mutations in HD and PEST domains. Mutations were seen in 4/10 adult patients (40%); in the pediatric cohort 2/5 (40%) had mutations both of which were in the PEST domain. Of the different mutations, two have been previously reported and the other four are novel. A high incidence of Notch-1 mutations has been seen; unlike other studies, a higher frequency of mutations was found in PEST domain. The current study also served to identify four novel mutants that add new insights into the genetic heterogeneity of T-ALL. More ongoing larger studies are warranted to elucidate the molecular pathogenesis of T-ALL that arises in this part of the world.

Key words: Notch-1 receptor; T-Cell acute lymphoblastic leukemia (T-ALL); Heterodimerization (HD) domain; Proline, glutamic acid, serine, threonine-rich (PEST) domain; India

Address correspondence to Dr. Bibhu R. Das, Super Religare Laboratories Ltd., Prime Square Building, Plot No 1, S. V. Road, Goregaon (W), Mumbai-400 062, India. Tel: +91-22-67801111; Fax: +91-22-67801212; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it

Volume 19, Number 1

Oncology Research, Vol. 19, pp. 1–11, 2010
0965-0407/10 $90.00 + .00
DOI: 10.3727/096504010X12767359114009
E-ISSN 1555-3906
Copyright © 2010 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Ultrastructural Changes in Rat Colon Following 1,2-Dimethylhydrazine-Induced Colon Carcinogenesis: Protection by Zinc

Vijayta Dani Chadha* and D. K. Dhawan*†

*Nuclear Medicine, Centre for Emerging Areas in Science and Technology, Panjab University, Chandigarh, India
†Department of Biophysics, Panjab University, Chandigarh, India

The present study evaluated the modulatory effects of zinc on 1,2-dimethylhydrazine (DMH)-induced ultrastructural changes in rat colon as well as on [3H]thymidine uptake and [14C]D-glucose metabolism. The rats were segregated into four groups: normal control, DMH treated, zinc treated, DMH + zinc treated. Initiation and induction of colon carcinogenesis was achieved through weekly subcutaneous injections of DMH (30 mg/kg body weight) for 8 and 16 weeks, respectively. Zinc was supplemented to rats at a dose level of 227 mg/L in drinking water, ad libitum for two different time durations of 8 and 16 weeks. The study revealed a significant decrease in zinc concentration in serum and colon following DMH treatment to rats, which upon zinc supplementation were recovered to near normal levels. A significant increase in in vitro [3H]thymidine uptake was observed following 16 weeks of DMH treatment. Further, a significant increase in the [14C]glucose turnover was observed following 8 and 16 weeks of DMH treatment. Simultaneous supplementation of zinc to DMH-treated rats for 16 weeks significantly decreased the uptake of [3H]thymidine and [14C]glucose when compared to DMH alone-treated rats. Changes in the ultrastructural architecture of colonic cells were evident following both treatment schedules of DMH; however, the changes were more distinguishable following 16 weeks of DMH treatment. The most obvious changes were seen in nuclear shape and disruption of cellular integrity, which upon zinc supplementation was appreciably improved. In conclusion, the study suggests positive beneficial effect of zinc against chemically induced colonic preneoplastic progression in rats.

Key words: Experimental carcinogenesis; Colon; Ultrastructure; Zinc

Address correspondence to D. K. Dhawan, Ph.D., Department of Biophysics, Panjab University, Chandigarh-160014, India. Tel: +91-172-2534121; Fax: +91-172?2534118; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 19, pp. 13–22, 2010
0965-0407/10 $90.00 + .00
DOI: 10.3727/096504010X12828372551713
E-ISSN 1555-3906
Copyright © 2010 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

RON and Cisplatin Resistance in Ovarian Cancer Cell Lines

Silvia Prislei,* Marisa Mariani,* Giuseppina Raspaglio,* Simona Mozzetti,* Flavia Filippetti,* Gabriella Ferrandina,† Giovanni Scambia,* and Cristiano Ferlini*

*Gynecologic Oncology Unit, Catholic University, 00168 Rome, Italy
†Department of Oncology, Catholic University, 86100 Campobasso, Italy

RON (recepteur d’origine nantais) tyrosine kinase receptor has revealed its tumorigenic potential in recent studies. RON was reported to be overexpressed in 55% of primary ovarian carcinoma samples and furthermore its activation increases cell motility and invasiveness. In this study, we investigated the correlation between RON expression and chemoresistance in ovarian cancer cells. In A2780 cells, a model featured by high chemosensitivity to cisplatin, stable overexpression of RON was able to reduce sensitivity to this agent, while incubation with a blocking anti-RON antibody (ID1) increased the cisplatin-induced growth inhibition effect. Moreover, we observed an increased RON expression both at the mRNA and protein level in A2780 cells made resistant to doxorubicin and paclitaxel (A2780ADR and TC1, respectively), two cell lines exhibiting a collateral resistance to cisplatin. OVCAR-3 cells, showing high levels of RON expression, also displayed inherent cisplatin resistance. The morphology observed in these resistant cells is consistent with a scattering phenotype and a RON-activated state. RON expression levels were monitored upon hypoxia. A 2.5-fold increase of RON expression was noticed in response to hypoxia in OVCAR-3 cells, in parallel with a decrease of E-cadherin mRNA. Altogether these results suggest an involvement of RON in the acquisition of cisplatin resistance and highlight the importance of this factor as a promising target for combination with cisplatin-based chemotherapy in ovarian cancer.

Key words: RON; Tyrosine kinase receptor; Ovarian cancer; Chemoresistance

Address correspondence to Cristiano Ferlini, Gynecologic Oncology Unit, Catholic University of Rome, L.go A. Gemelli 8, 00168 Rome, Italy. Tel/Fax: 39-06 35508736; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 19, pp. 23–33, 2010
0965-0407/10 $90.00 + .00
DOI: 10.3727/096504010X12828372551759
E-ISSN 1555-3906
Copyright © 2010 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

AP-1-Dependent miR-21 Expression Contributes to Chemoresistance in Cancer Stem Cell-Like SP Cells

Aya Misawa,*‡ Ryohei Katayama,* Sumie Koike,* Akihiro Tomida,† Toshiki Watanabe,‡ and Naoya Fujita*

*Division of Experimental Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan
†Division of Genome Research, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan
‡Laboratory of Tumor Cell Biology, Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan

The side population (SP) of cancer cells is a minor population of cells that has been identified in a variety of cancers and harbors many cancer stem cell (CSC)-like properties, such as self-renewal potential, tumor-forming capacity, and chemoresistant phenotype. CSCs are regarded as the root of cancer origin and recurrence. Thus, new therapeutic approaches targeting these malignant cells have become the topic of ongoing research. However, the chemoresistant phenotype of CSCs makes it difficult to increase their sensitivity to anticancer drugs and to decrease the rate of cancer recurrence in patients. In this study, we analyzed the chemoresistant phenotype of SP cells derived from various cancer cell lines. Microarray analysis discriminated differential gene expression profiles between SP and non-SP cells. MicroRNA-21 (miR-21) and its upstream regulator activator protein-1 (AP-1), composed of c-Jun and c-Fos family transcription factors, were found to be frequently upregulated in SP cells. Downregulation of tumor suppressor programmed cell death 4, one of the miR-21 target gene products, confirmed miR-21 overexpression in SP cells. Treatment of the cells with the AP-1 inhibitor SP600125 attenuated miR-21 levels and increased topotecan sensitivity. Furthermore, specific inhibition of miR-21 by an anti-miR-21 locked nucleic acid increased drug sensitivity and decreased colony forming ability. These findings define the critical role of miR-21 in maintenance of the chemoresistant phenotype of SP cells. Targeting miR-21 may provide a new strategy for cancer therapy by impairing resistance to chemotherapy in CSCs.

Key words: MicroRNA (miRNA); Side population (SP); Cancer stem cell (CSC); Chemoresistance

Address correspondence to Naoya Fujita, Division of Experimental Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan. Tel: +81-3-3570-0468; Fax: +81-3-3570-0484; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 19, pp. 35–43, 2010
0965-0407/10 $90.00 + .00
DOI: 10.3727/096504010X12828372551812
E-ISSN 1555-3906
Copyright © 2010 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

The Insulin-Like Growth Factor-1 Receptor Kinase Inhibitor, NVP-ADW742, Suppresses Survival and Resistance to Chemotherapy in Acute Myeloid Leukemia Cells

Yanli He,1 Jiahua Zhang,1 Jine Zheng, Wen Du, Hong Xiao, Wei Liu, Xiaoqing Li, Xiangjun Chen, Lin Yang, and Shiang Huang

Center for Stem Cell Research and Application, Institute of Hematology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

Deregulation of insulin-like growth factor-1 receptor (IGF-1R) is closely associated with malignant transformation and tumor cell survival in various cancers. We found that IGF-1R expression level in leukemia cells positively correlated with the percentage of blast in bone marrow from de novo acute myeloid leukemia (AML) patients. Moreover, we showed that NVP-ADW742, a novel small weight molecular inhibitor of IGF-1R, could induce apoptosis in both HL-60 cell line and primary AML blasts. However, no significant alteration of cell cycle was observed in HL-60 cells. Further studies revealed that NVP-ADW742 induced Akt dephosphorylation, which might subsequently induce p38 phosphorylation and decrease antiapoptotic protein Bcl-2 expression in HL-60 cells. Finally, we demonstrated that NVP-ADW742 could synergize with Ara-C to induce the kill in a subset of drug-resistant AML specimens. We suggested that IGF-1R targeting might be therapeutically beneficial for some AML patients.

Key words: NVP-ADW742; Insulin-like growth factor-1 receptor (IGF-1R); Acute myeloid leukemia (AML); Apoptosis

1These authors provided equal contribution to this work.
Address correspondence to Shiang Huang, M.D., Center for Stem Cell Research and Application, Union Hospital,1277 Jiefang Avenue, Wuhan 430022, China. Tel: +86 027 85726015; Fax: +86 027 85729267;E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 19, pp. 45–54, 2010
0965-0407/10 $90.00 + .00
DOI: 10.3727/096504010X12828372551867
E-ISSN 1555-3906
Copyright © 2010 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Review

β-Adrenergic Receptors in Cancer: Therapeutic Implications

Mario Pérez-Sayáns,* José Manuel Somoza-Martín,* Francisco Barros-Angueira,† Pilar Gayoso Diz,‡ José Manuel Gándara Rey,* and Abel García-García*

*Entrerríos s/n, Santiago de Compostela, Spain
†Unidad de Medicina Molecular-Fundación Pública Galega de Medicina Xenómica, Edificio de Consultas planta-2, Hospital Clinico Universitario, Santiago de Compostela, Spain
‡Department of Clinical Epidemiology, Edificio de Consultas planta 0, Complejo Hospitalario Universitario de Santiago, Santiago de Compostela, Spain

The β-adrenergic receptors transduce catecholamine signals to the G protein, which through a cascade of chemical reactions in cells generates highly specific parallel signals. The β2-adrenergic receptor (ADRB2) is the most involved in the carcinogenic processes. Previous studies have determined the relationship of ADRB2 with various aspects related to cancer. Basically, it seems to be related with cell proliferation and apoptosis, chemotaxis, development of metastasis and tumor growth, and angiogenesis. The purpose of this review is to update the implications of these receptors in the pathogenesis of cancer and study the possible application of agonist drugs and/or antagonists in antitumor therapy.

Key words: β-Adrenergic receptors; ADRB2; β2-Adrenergic receptor; Chemotaxis; Apoptosis; β-Adrenergic agonist; β-Adrenergic antagonist

Address correspondence to Mario Pérez-Sayáns, Ph.D., D.D.S., Facultad de Odontología, Entrerríos s/n, Santiago de Compostela C.P. 15782, Spain. Tel: 0034626233504; Fax: 0034986295424; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it