alexa Progesterone inhibition of MDM2 p90 protein in MCF-7 human breast cancer cell line is dependent on p53 levels | OMICS International
ISSN: 1747-0862
Journal of Molecular and Genetic Medicine
Make the best use of Scientific Research and information from our 700+ peer reviewed, Open Access Journals that operates with the help of 50,000+ Editorial Board Members and esteemed reviewers and 1000+ Scientific associations in Medical, Clinical, Pharmaceutical, Engineering, Technology and Management Fields.
Meet Inspiring Speakers and Experts at our 3000+ Global Conferenceseries Events with over 600+ Conferences, 1200+ Symposiums and 1200+ Workshops on
Medical, Pharma, Engineering, Science, Technology and Business

Progesterone inhibition of MDM2 p90 protein in MCF-7 human breast cancer cell line is dependent on p53 levels

Moussa Alkhalaf 1*, Abdalla M El-Mowafy2 and Laila A Abou-Zeid3

1Department of Biochemistry, Faculty of Medicine, Mansoura University, Egypt

2Department of Applied Therapeutics, Faculty of Pharmacy, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait.

3Department of Chemistry, Faculty of Pharmacy, Mansoura University, Egypt

*Corresponding Author:
Moussa Alkhalaf
Tel: +965 5319489
Fax: +965 5338908
Email: [email protected]

Received date: 11 April 2005; Revised date: 16 June 2005; Accepted daate: 20 June 2005, Available online 19 August 2005; Published date: 19 August 2005

© Copyright: Moussa Alkhalaf et al

Visit for more related articles at Journal of Molecular and Genetic Medicine

Abstract

The mdm2 gene encodes several protein isoforms with different molecular weights (p90, p80, p76 and p57). MDM2 p90 (usually considered to be the major MDM2 protein) binds to and inactivates P53. We have recently shown that growth inhibition of MCF-7 human breast cancer cells by progesterone is associated with P53 down-regulation. In this work, we analyzed the expression pattern of MDM2 proteins in three human breast cancer cell lines by western blotting with anti-MDM2 antibodies. We found a prominent expression of MDM2 p57 protein in cell lines which have non-functional P53 protein (T47D and MDA-MB-231) as compared to the p90, p80 isoforms, whereas p90 was the major protein isoform in MCF-7 cells that contain functional P53 protein. When MCF-7 cells were treated with 100 nM of progesterone, MDM2 p90 was inhibited but the highly expressed MDM2 p57 isoform was not. The inhibition of MDM2 p90 protein by progesterone was abrogated in MCF-7 cells transfected with a P53 expressing vector. To our knowledge, this is the first report linking progesterone-induced growth inhibition with down-regulation of the MDM2 protein. We present evidence that reestablishing of P53 expression by transient transfection of P53 cDNA in these cells enhances the expression level of MDM2 p90 isoform. The data indicate that expression of MDM2 p90 is regulated through a P53-dependent pathway in response to progesterone

Keywords

MDM2, isoforms, p53, p90, progesterone, MCF-7, breast cancer

Introduction

The mdm2 gene was originally cloned as an amplified gene on a murine double-minute chromosome in the tumorigenic 3T3DM murine cell line (Fakharzadeh et al, 1991). The corresponding human mdm2 gene was also subsequently identified (Oliner et al, 1992). MDM2 expression is controlled at the transcriptional level from P53-independent (P1) and P53-responsive (P2) promoters (Zauberman et al, 1995), both encoding a 90 kDa full length MDM2 (p90) protein (Brown et al, 1999). In addition, MDM2 proteins of smaller sizes have been identified (Olson et al, 1993; Perry et al, 2000; Bartel et al, 2002). These differently sized proteins arise through either proteolytic cleavage (Pochampally et al, 1998), internal translational initiation (Saucedo et al, 1999) or alternative splicing (Sigalas et al, 1996; Matsumoto, 1998). Although the biochemical functions of these small proteins have not yet been determined, the MDM2-p90 isoform binds to and inactivates P53 tumor suppressor protein suggesting that MDM2 can function as a negative feedback regulator of P53 (Momand et al, 1992; Barak et al, 1993). Lukas et al (2001) suggested that MDM2 expression is altered in invasive breast cancer and is associated with more aggressive disease. We have recently demonstrated that the progesterone-induced growth inhibition of the MCF-7 human breast cancer cell line was associated with down-regulation of P53 endogenous levels (Alkhalaf and El-Mowafy, 2003). Because the regulation of MDM2 expression by P53 has been proposed by several authors to be the mechanism by which P53 balances its own activity (Juven et al, 1993; Midgley and Lane, 1997; Prives, 1998), we hypothesized that the decrease in P53 levels seen in MCF-7 cells treated with progesterone would affect MDM2 expression. We report here that in MCF-7 human breast cancer cells treated with progesterone, MDM2 p90 but not MDM2 p57 is down-regulated. To confirm the involvement of P53 in this down-regulation of MDM2, MCF-7 cells were transiently transfected with a P53 expression vector (Alkhalaf and El-Mowafy, 2003). Overexpression of P53 in MCF-7 cells stimulated the MDM2 expression and abrogated the effect of progesterone. The data suggest that expression of MDM2 p90 is regulated via a P53-dependent pathway in MCF-7 human breast cancer cells treated with progesterone.

Materials and Methods

The breast cancer cell lines MCF7, T47D, and MDA-MB231 were kindly provided by Bohdan Wasylyk (IGBMC Core Facility, Strasbourg, France). The MCF-7 cells contain functional P53 protein localized at the nucleus (Wasylyk et al, 1999) and classified as progesterone and estrogen receptor positive. The T47D cells have a mutated type of P53 which is localized in the cytoplasm (Schafer et al, 2000) and contain both estrogen and progesterone receptors. The MDA-MB231 cells have non-functional P53 protein (Toillon et al, 2002) and have no functional progesterone and estrogen receptors. The cells were grown in RPMI1640 medium (Gibco BRL) supplemented with 5% fetal bovine serum, glutamine and gentamicin and maintained in a 5% CO2 humidified atmosphere in a 37 °C incubator.

Western Blot Analysis

Cells were washed twice with PBS buffer then the preheated (95°C) lysis buffer [20 mM Tris-HCl pH 7.4, 20 mM dithiothreitol (DTT), 2 mM EDTA (sodium salt), 1% (v/v) Triton X-100, 1% (v/v) NP40, 1% (w/v) sodium deoxycholate, 1 mM sodium pyrophosphate, 1 mM sodium orthovandate (prepared in Tris buffer) and 1 mM phenylmethylsulphonyl-fluoride] was added directly to the cell monolayer. The cells were scraped and mixed with a rubber policeman, transferred to Eppendorf tubes and centrifuged at 13000 x g for 5 min. The resulting supernatant was saved and the protein was determined by the Bradford method. Extracts were boiled for 3 min in 2 x SDS buffer. Equal amounts of protein were loaded on 10% (w/v) polyacrylamide gels according to the method of Laemmli and then electrotransferred onto nitro-cellulose membranes. The blots were incubated first with anti-MDM2 (Ab-1, clone IF2) monoclonal antibody (Oncogene Research Product, Calbiochem). The antibody is directed against the N-terminal fragment between amino acid residues 26-169 of human MDM2 (Fakharzadeh et al, 1991) then incubated with peroxidase-conjugated anti-mouse IgG (Jackson Laboratory, USA) at 1/2000 dilution. Immunoreactive bands were visualized by incubation with luminol (according to manufacturer's instructions; ECL Western blotting detection system from Amersham). The blots were stripped and hybridized with P53 (DO1) monoclonal antibodies (Oncogene Research, Cambridge, MA, USA) and processed as for the MDM2 antibodies. The TATA- Binding Protein (TBP) monoclonal antibody was used as a loading control (kindly provided by IGBMC Core Facility, Illkirch, France). Another MDM2 antibody was used, MDM2 (C-18) purchased from Santa Cruz Biotechnology (California, USA). It is an affinity purified rabbit polyclonal antibody raised against a peptide mapping within the carboxyl terminal domain of MDM2 of human origin. A prestained SDS-PAGE molecular weight protein standards (low range) is used to estimate the molecular weights of proteins ((Bio-Rad, UK).

Transient transfection of MCF-7 with P53 cDNA expression vector

MCF-7 cells were maintained in RPMI1640 medium + 5% FBS + antibiotics at 37°C with 5% (v/v) CO2 in 36 mm plates (6-well cluster, Nunc, Roskilde, Denmark). They were transfected either with 3 μg CMV expression vector (pcDNA3, obtained from Invitrogen, Paisley, UK) or with 3 μg CMV vector containing human P53 cDNA (kindly provided by the IGBMC core facility, Illkirch, France) by using lipofectamine (Gibco-BRL, Paisley, UK). MCF-7 cells that overexpress P53 as well as the control cells (transfected with the empty vector) were treated with vehicle alone or with 100 nM of progesterone for 24 hr. The total protein extracts were prepared and tested with DO-1, IF2 and TBP monoclonal antibodies as indicated above.

Results

Prominent expression of MDM2 p57 protein in human cancer cell lines

The expression of MDM2 proteins in MCF7, T47D, and MDA-MB231 human breast cancer cell lines was analyzed by Western blotting with anti-MDM2 (Ab-1) monoclonal antibody. Figure 1 shows that, with this antibody, four MDM2 isoforms were detected, the p57, p76, p80, and p90 kDa in all three cell lines. A prominent expression of MDM2 p57 protein as compared to the p90, p80 or p76 was observed in the three cell lines used in this study. MDM2 p90 protein level was dependent on p53 status in the cells. In MCF-7 cells that contained functional P53 protein, the endogenous MDM2 p90 protein level was higher than these in T47D and MDA-MB 230 cell lines (both have mutated P53 proteins). In contrast, MDM2 p57 appeared to be lower in MCF-7 as compared to its levels in the cells which have mutated P53. The high level of MDM2 p57 was observed in other breast cancer cells, a normal breast cell line and in other types of cancer cell lines (data not shown).

molecular-genetic-medicine-Endogenous-levels

Figure 1. Endogenous levels of P53 and MDM2 isoforms in human breast cancer cell lines. Endogenous levels of MDM2 proteins (p90, p80, p57) and P53 proteins in human breast cancer cell lines MDA-MB231 (lane 1); T47D (lane 2), MCF-7 (lane 3). 100 μg of total protein extract were analyzed by 10% SDSPAGE, blotted on nitrocellulose membranes and probed with antibodies against MDM2 (IF2), P53 (DO1) and TBP (3G3). Four isoforms of MDM2 were detected and the most abundant is the p57 isoform. P53 protein was detected in all cell lines with different levels. TBP was used as a loading control since it shows the same level in all cell lines.

Progesterone inhibits MDM2 p90 in MCF-7 human breast cancer cell line

The MCF-7 cell line was used in this experiment because it has high levels of the four MDM2 isoforms and because we had already shown that progesterone down-regulated P53 protein in these cells (Alkhalaf and El-Mowafy, 2003). We investigated whether the P53 inhibition in this cell line would affect the endogenous levels of MDM2 proteins. When MCF-7 cells are treated with 100 nM of progesterone, expression of p90 was specifically inhibited, unlike that of the highly expressed p57 isoform or the TBP protein (Figure 2).

molecular-genetic-medicine-protein-progesterone

Figure 2. Inhibition of MDM2 p90 protein by progesterone in MCF-7 human breast cancer cells. MCF7 cells were cultured in 5% fetal bovine serum and treated with100 nM of progesterone, harvested at the indicated times. Cellular extracts (100 μg) were analyzed by Western blots for levels of MDM2 (C- 18 antibody) and TBP (3G3).

P53 Overexpression stimulates MDM2 expression in MCF-7 human breast cancer cells

The observation that progesterone simultaneously inhibited endogenous MDM2 (Figure 2) and P53 (Alkhalaf and El-Mowafy, 2003) in MCF-7 cells prompted us to check the consequences of re-establishing the P53 expression in the cells by exogenous expression using transient transfection experiments. MCF-7 cells were transfected with expression vector (3 μg/well) for CMV vector and CMV vector containing human P53 cDNA. The cells were treated with vehicle or with 100 nM of progesterone for 24 hr. Western blot analysis was used to estimate the P53 levels achieved by transient transfection. CMV- transfected MCF-7 without progesterone treatment showed normal levels of P53, MDM2 p90 and MDM2 p57. When CMV-transfected MCF-7 cells were treated with 100 nM of progesterone, both MDM2 p90 and P53 were inhibited, unlike the MDM2p57 isoform. MCF-7 cells transfected with CMV+P53 vector showed approximately three fold higher P53 levels than CMV transfected cells (Figure 3) as revealed by densitometry. In these P53 overexpressing MCF-7 cells, the MDM2 p90 level was elevated to reach approximately the same level observed in the CMV transfected MCF7 cells without progesterone treatment. The increase in MDM2 p90 level in MCF-7 cells that overexpress P53 is associated with progesterone treatment suggesting that p53 reestablishing p53 expression enhances the expression of MDM2 p90 and that this increase in MDM2 level is progesterone-dependent.

molecular-genetic-medicine-Western-blotting-analysis

Figure 3. The inhibition of MDM2 p90 protein by progesterone was abrogated in MCF-7 cells transfected with a p53 expressing vector: MCF-7 cells were transfected with expression vector (3 μg/well) for CMV vector and CMV vector containing human P53 cDNA. The cells were treated with vehicle or with 100 nM of progesterone (P) for 24 hours. 20 Og of extracts were subjected to Western blotting analysis to determine the relative amounts of P53, MDM2 p90, MDM2 p57 and TBP (used as a loading control) proteins. MCF-7 cells transfected with CMV-P53 vector contained over three fold of P53 than CMV transfected cells. The cells showed increase in MDM2 p90 but not in MDM2 p57 protein levels. The increase in the MDM2 p90 in response to P53 overexpression has the same magnitude observed in cells not treated with progesterone.

Discussion

More than 40 different splice variants of MDM2 transcripts have been identified both in tumors and normal tissues (Gudas et al, 1995; Lukas et al, 2001; Bartel et al, 2002; Phelps et al, 2003). At the protein level at least five MDM2 proteins (p90, p80, p74/76, p70, p57/60) have been described (Oslon et al, 1993; Haider et al, 1997; Pochampally et al, 1998; Pochampally et al, 1999; Saucedo et al, 1999; Bartl et al, 2003). It was demonstrated that these differently-sized MDM2 isoforms may arise through either proteolytic cleavage (Pochampally et al, 1998), internal translational initiation (Saucedo et al, 1999) or alternative splicing (Sigalas et al, 1996; Matsumoto et al, 1998). Although the biochemical functions of these proteins have not yet been determined, their existence suggests that MDM2 may be involved in additional unknown functions.

The expression of MDM2 is known to be induced by P53 as Landers et al. 1997 demonstrated that the high level of mdm2 overexpression in human tumor cells containing elevated levels of wild-type P53 resulted from enhanced translation at the p53-responsive promoter region of the mdm2 gene (Landers et al, 1997). Recent evidence has shown that MDM2 expression can also be regulated via P53-independent pathways (Phelps et al, 2003). Our data show that in cells with functional P53 proteins, endogenous MDM2 p90 was the major MDM2 protein isoform and that cells with a mutated P53 gene showed very low levels of the MDM2 p90 protein. The present data show also that progesterone down-regulates the endogenous level of MDM2 p90. This down-regulation of MDM2 p90 may be associated with down-regulation of the endogenous P53 level observed in the same conditions (Alkhalaf and El-Mowafy, 2003). By contrast, re-establishing the P53 endogenous expression in MCF-7 by transient expression led to elevation of MDM2 p90 indicating the possible involvement of the P53 pathway in the regulation of MDM2 p90.

Overexpression of the MDM2 proteins is often observed in breast cancer tissues and cell lines (Sheikh et al, 1993; McCann et al, 1995; Pinkas et al, 1999). Bueso-Ramos et al (Bueso-Ramos et al, 1996) suggested that MDM-2 p57 protein represents the main MDM-2 protein altered in breast carcinomas: they found MDM-2 overexpression in 15 of 21 breast carcinoma tissue samples. Ten of these fifteen cases overexpressed MDM2 p57 protein, while two cases overexpressed both MDM2 p57 and MDM2 p90, and three cases overexpressed only MDM2 p90. However, the status of the P53 gene in the tumors overexpressing the MDM2 p57 was not reported. Our data show that MDM2 p57 is the predominant isoform in cancer cells that have mutations in the P53 gene. However, further studies are required to fully understand the correlation between the expression of the different forms of MDM2 proteins and the P53 status in breast cancer tumors.

Acknowledgments

We thank Professor Christopher H. J. Ford for his critical reading of the manuscript and Maya Bakir and Lilly Verghese for technical assistance. This work was supported by grant MB 04/04 awarded by Kuwait University Research Administration.

Statement of Competing Interests

The authors declared no competing interests.

Acknowledgments

  1. Alkhalaf M, El-Mowafy A. Overexpression of wild-type P53 gene renders MCF-7 breast cancer cells more sensitive to the antiproliferative effect of progesterone. J Endocrinol. 2003;179:55-62.
  2. Barak Y, Juven T, Haffner R, Oren M. mdm2 expression is induced by wild type p53 activity. EMBO J. 1993;12:461-468.
  3. Bartel F, Taubert H, Harris LC. Alternative and aberrant splicing of MDM2 mRNA in human cancer. Cancer Cell. 2002;2:9-15.
  4. Bartl S, Ban J, Weninger H, Jug G, Kovar H. A small nuclear RNA, hdm365, is the major processing product of the human mdm2 gene. Nucleic Acids Res. 2003;31:1136-1147.
  5. Brown CY, Mize GJ, Pineda M, George DL, Morris DR. Role of two upstream open reading frames in the translational control of oncogene mdm2. Oncogene. 1999;18:5631-5637.
  6. Bueso-Ramos CE, Manshouri T, Haider MA, Yang Y, McCown P, Ordonez N, Glassman A, Sneige N, Albitar M. Abnormal expression of MDM-2 in breast carcinomas. Breast Cancer Res Treat. 1996;37:179-188.
  7. Fakharzadeh SS, Trusko SP, George DL. Tumorigenic potential associated with enhanced expression of a gene that is amplified in a mouse tumor cell line. EMBO J. 1991;10:1565-1569.
  8. Gudas JM, Nguyen H, Klein RC, Katayose D, Seth P, Cowan KH. Differential expression of multiple MDM2 messenger RNAs and proteins in normal and tumorigenic breast epithelial cells. Clin Cancer Res. 1995;1:71-80.
  9. Haider MA, El-Hajj H, Bueso-Ramos CE, Manshouri T, Glassman A, Keating MJ, Maher A. Expression profile of MDM-2 proteins in chronic lymphocytic leukemia and their clinical relevance. Am J Hematol. 1997;54:189-195.
  10. Juven T, Barak Y, Zauberman A, George DL, Oren M. Wild type P53 can mediate sequence-specific transactivation of an internal promoter within the mdm2 gene. Oncogene. 1993;8:3411-3416.
  11. Landers JE, Cassel SL, George DL. Translational enhancement of mdm2 oncogene expression in human tumor cells containing a stabilized wild-type P53 protein. Cancer Res. 1997;57:3562-3568.
  12. Lukas J, Gao DQ, Keshmeshian M, Wen WH, Tsao-Wei D, Rosenberg S, Press MF. Alternative and aberrant messenger RNA splicing of the mdm2 oncogene in invasive breast cancer. Cancer Res. 2001;61:3212-3219.
  13. Matsumoto R, Tada M, Nozaki M, Zhang CL, Sawamura Y, Abe H. Short alternative splice transcripts of the mdm2 oncogene correlate to malignancy in human astrocytic neoplasms. Cancer Res. 1998;58:609-613.
  14. McCann AH, Kirely A, Carney DN, Corbally N, Magee HM, Keating G, Dervan PA. Amplification of the MDM2 gene in human breast cancer and its association with MDM2 and P53 protein status. Brit J Cancer. 1995;71:981-985.
  15. Midgley CA, Lane DP. P53 stability in tumour cells is not determined by mutation but is dependent on Mdm2 binding. Oncogene. 1997;15:1179-1189.
  16. Momand J, Zambetti GP, Olson DC, George D, Levine AJ. The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell. 1992;69:1237-1245.
  17. Oliner JD, Kinzler KW, Meltzer PS, George DL, Vogelstein B. Amplification of a gene encoding a P53-associated protein in human sarcomas. Nature. 1992;358:80-83.
  18. Olson DC, Marechal V, Momand J, Chen G, Romocki C, Levine AJ. Identification and characterization of multiple mdm-2 proteins and mdm-2-p53 protein complexes. Oncogene. 1993;8:2353-2360.
  19. Perry ME, Mendrysa SM, Saucedo LJ, Tannous P, Holubar M. p76(MDM2) inhibits the ability of p90(MDM2) to destabilize p53. J Biol Chem. 2000;275:5733-5738.
  20. Phelps M, Darley M, Primorse JN, Blaydes JP. P53-independent activation of the hdm2-P2 promoter through multiple transcription factor response elements results in elevated hdm2 expression in estrogen receptor alpha-positive breast cancer cells. Cancer Res. 2003;63:2616-2623.
  21. Pinkas J, Naber SP, Butel JS, Medina D, Jerry DJ. Expression of MDM2 during mammary tumorigenesis. Int J Cancer. 1999;81:292-298.
  22. Pochampally R, Fodera B, Chen L, Lu W, Chen J. Activation of an MDM2-specific caspase by p53 in the absence of apoptosis. J Biol Chem. 1999;274:15271-15277.
  23. Pochampally R, Fodera B, Chen L, Shao W, Levine EA, Chen JA. 60 kd MDM2 isoform is produced by caspase cleavage in non-apoptotic tumor cells. Oncogene. 1998;17:2629-2636.
  24. Prives C. Signaling to P53: breaking the MDM2-P53 circuit. Cell. 1998;95:5-8.
  25. Saucedo LJ, Myers CD, Perry ME. Multiple murine double minute gene 2 (MDM2) proteins are induced by ultraviolet light. J Biol Chem. 1999;274:8161-8168.
  26. Schafer JM, Lee ES, O'Regan RM, Yao K, Jordan VC. Rapid development of tamoxifen-stimulated mutant P53 breast tumors (T47D) in athymic mice. Clin Cancer Res. 2000;11:4373-4380.
  27. Sheikh MS, Shao ZM, Hussain A, Fontana JA. The P53-binding protein MDM2 gene is differentially expressed in human breast carcinoma. Cancer Res. 1993;53:3226-3228.
  28. Sigalas I, Calvert AH, Anderson JJ, Neal DE, Lunec J. Alternatively spliced mdm2 transcripts with loss of p53 binding domain sequences: transforming ability and frequent detection in human cancer. Nature Med. 1996;2:912-917.
  29. Toillon RA, Chopin V, Jouy N, Fauquette W, Boilly B, LeBourhis X. Normal breast epithelial cells induce p53-dependent apoptosis and p53-independent cell cycle arrest of breast cancer cells. Breast Cancer Res Treat. 2002;71:269-280.
  30. Wasylyk C, Salvi R, Argentini M, Dureuil C, Delumeau I, Abecassis J, Debussche L, Wasylyk B. p53 mediated death of cells overexpressing MDM2 by an inhibitor of MDM2 interaction with p53. Oncogene. 1999;18:1921-1934. 1999.
  31. Zauberman A, Flusberg D, Haupt Y, Barak Y, Oren M. A functional p-53 responsive intronic promoter is contained within the human mdm2 gene. Nucleic Acids Res. 1995;23:2584-2592.
Select your language of interest to view the total content in your interested language
Post your comment

Share This Article

Relevant Topics

Recommended Conferences

Article Usage

  • Total views: 11724
  • [From(publication date):
    August-2005 - Dec 17, 2017]
  • Breakdown by view type
  • HTML page views : 7960
  • PDF downloads : 3764
 

Post your comment

captcha   Reload  Can't read the image? click here to refresh

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri & Aquaculture Journals

Dr. Krish

[email protected]

1-702-714-7001Extn: 9040

Biochemistry Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

[email protected]

1-702-714-7001Extn: 9042

Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001Extn: 9040

Clinical Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Engineering Journals

James Franklin

[email protected]

1-702-714-7001Extn: 9042

Food & Nutrition Journals

Katie Wilson

[email protected]

1-702-714-7001Extn: 9042

General Science

Andrea Jason

[email protected]

1-702-714-7001Extn: 9043

Genetics & Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Materials Science Journals

Rachle Green

[email protected]

1-702-714-7001Extn: 9039

Nursing & Health Care Journals

Stephanie Skinner

[email protected]

1-702-714-7001Extn: 9039

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

Ann Jose

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

[email protected]

1-702-714-7001Extn: 9042

 
© 2008- 2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version