alexa Role Of Nuclear Pore Protein NUP62 In Ovarian Cancer Cisplatin Chemoresistance
ISSN: 2161-1025

Translational Medicine
Open Access

Like us on:
OMICS International organises 3000+ Global Conferenceseries Events every year across USA, Europe & Asia with support from 1000 more scientific Societies and Publishes 700+ Open Access Journals which contains over 50000 eminent personalities, reputed scientists as editorial board members.

Open Access Journals gaining more Readers and Citations

700 Journals and 15,000,000 Readers Each Journal is getting 25,000+ Readers

This Readership is 10 times more when compared to other Subscription Journals (Source: Google Analytics)

Share This Page

Additional Info

Loading
Loading Please wait..
 

2nd International Conference on Translational & Personalized Medicine
August 05-07, 2013 Holiday Inn Chicago-North Shore, IL, USA

Tamara Kalir
Accepted Abstracts: Transl Med
DOI: 10.4172/2161-1025.S1.010
Abstract
Objective: While not the most common of the gynecologic malignancies, ovarian cancer is the number one cause of death from gynecologic cancer in American women. Ovarian cancers high mortality rate is a result of: i) pathogenesis being incompletely understood; ii) early-stage disease being asymptomatic, iii) lack of a cost-effective screening test, and iv) most patients while showing initial good response to surgery & chemotherapy, eventually develop chemoresistance and disease recurrence. We have previously reported that altered NUP62 induces dormancy in ovarian cancer cell lines, and confers resistance to cisplatin. We have explored the chemoresistance mechanism further. Materials & Methods: Ovarian cancer cell lines A2780 (cisplatin sensitive) and CP70 (cisplatin resistant) were used for in vitro experiments. Activated form of proline-rich tyrosine kinase (PYK2) was assessed via antibody to phosphoY402 site (Cell Signaling Technology). Colony forming assays used PYK2 inhibitor PF-562271 (Selleckchem). Tyrosine phosphatase inhibitor pervanadate was used to assess subcellular distribution of phosphorylated Y422 NUP62 via immunofluorescence microscopy. The work on human tumors was approved by the Institutional Review Board. Tissue microarrays (TMAs) were created by taking four needle- core biopsies sized at 0.6 mm, from each paraffin-embedded tissue block guided by the hematoxylin-eosin-stained (H&E) slide. The cases were collected from the Surgical Pathology Archives at The Icahn (at Mount Sinai) School of Medicine. Three-micron thick slices were cut from the TMA blocks, placed on 3-aminopropyltriethoxysilane-coated slides to enhance adhesion. Slides were subjected to manual deparaffination and rehydrated. Immunohistochemistry was performed using anti- phosphorylated tyrosine 422 residue (Y422) of the NUP62 protein according to standard procedures. Samples were analyzed by scoring each case for intensity of staining (0, 1+ =mild staining, 2+=moderate staining, or 3+=strong staining), extent of staining (0, 25%, 50%, 75%, 100%), and distribution of staining (cytoplasmic, nuclear / nuclear membrane). Kaplan Meier analysis was performed. Results: In vitro assays with cisplatin showed greater activated PYK2 in CP70 cells than A2780 cells, which redistributed to the nucleus after 18 hours in culture. When exposed to cisplatin in the presence of PYK2 inhibitor PF-562271, regrowth of remnant CP70 cells was diminished. Treatment of cultured cells with protein tyrosine phosphatase inhibitor pervanadate resulted in movement of phosphorylated NUP62 from the nuclear membrane into the cytoplasm. TMA results: Eighty-nine patients? cases met selection criteria. Of these, average patient age was 59 years old, 81% were Caucasian, 86% had optimal cytoreduction, 54% showed platinum resistance, 67% experienced tumor recurrence, 24.9% showed 5-year progression free survival, and 50.6% showed 5-year overall survival. Histologically, 80% of cases were serous carcinomas, and 88% were high-grade malignancies. Tumors with nuclear distribution of phospho-Y422-NUP62 showed greater progression-free survival than those with cytoplasmic NUP (P=0.0069). Conclusions: Redistribution of activated PYK2 to the nucleus may contribute to cisplatin resistance. Redistribution of PYK2 may contribute to the growth recovery of quiescent cisplatin resistant cells. Activation and translocation of PYK2 induces phosphorylation of NUP62 at Y422 and its release into the cytoplasm. In vitro results are mirrored by TMA studies in human samples and suggest that PYK2 signals promote resistance to platinum treatment and regrowth of tumor cells.
image PDF   |   image HTML
 
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
adwords