Accession Number:

ADA426086

Title:

Developing Inhibitors of Ovarian Cancer Progression by Targeted Disruption of the Gamma-Synuclein Activated Migratory and Survival Signaling Pathways

Descriptive Note:

Annual rept. 1 Apr 2003-31 Mar 2004

Corporate Author:

FOX CHASE CANCER CENTER PHILADELPHIA PA

Personal Author(s):

Report Date:

2004-04-01

Pagination or Media Count:

19.0

Abstract:

Synucleins are a family of highly conserved small proteins that are normally expressed predominantly in neurons. Very little is known about the physiological functions of the synucleins. We have reported that g-synuclein also known as BCSG1 is dramatically up-regulated in the vast majority 70 of late-stage breast and ovarian cancers Bruening, et al., 2000. When over-expressed, g-synuclein significantly stimulates cell proliferation and metastasis in some breast cancer cell lines. We have shown that DNA hypomethylation is a common mechanism underlying the abnormal expression of this gene in tumor cells Gupta et al., 2003 and hypothesize that g-synuclein may be a proto-oncogene and that abberant expression of this protein may contribute to the development and progression of ovarian cancer. We also found that g-synuclein can promote cancer cell survival and inhibit stress- and chemotherapy drug-induced apoptosis by modulating MAPKs. Specifically, over-expression of g-synuclein lead to constitutive activation of ERK12, and down- regulation of JNK1 in response to a host of environmental stress signals, including Uv, heat shock, sodium arsenate, nitric oxide and chemotherapeutic drugs Pan, Z-Z, et al., 2002. Because of its high frequency of expression in late- stage ovarian cancers, we hypothesized that g-synuclein may be a promising target for cancer therapy.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE