Analysis of Pro-Apoptotic and Antiangiogenic Activity of CC3 in Breast Cancer Cells
Abstract
CC3 was identified as a metastasis suppressor protein in vivo. This laboratory demonstrated that CC3 impairs apoptotic resistance of cells derived from aggressive tumors and inhibits production of angiogenic factors by these cells. CC3 expression was introduced into two breast carcinoma cell lines derived from metastatic tumors and expressing very low levels of this protein. Expression of exogenous CC3 lead to enhancement of their apoptotic responses to growth factors withdrawal and treatment with cytotoxic drugs. However, there was no effect of CC3 expression on angiogenic activity of breast cancer cells which was very low even prior to introduction of CC3. Because CC3 protein has no significant homologies to other known proteins, we have conducted analysis of cellular proteins that interact with CC3. Mass-spectrometric analysis of isolated protein revealed an amazing consistency among types of proteins that form complexes with CC3. Out of seven proteins identified, five belong to the family of importins of beta class and one is exportin, i.e. all these are proteins that serve as nuclear transport receptors. This amazing specificity in CC3 interactions pointed to a possibility that CC3 might be a factor involved in regulation of nuclear transport. Indeed, CC3 associates with nuclear envelope. Future work will focus on the mechanism through which CC3, via its possible role in nuclear transport, influences apoptosis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2002
- Accession Number
- ADA407408
Entities
People
- Emma Shtivelman
- Frank King
Organizations
- University of San Francisco