Enhanced sensitivity to cytochrome c-induced apoptosis mediated by PHAPI in breast cancer cells.

Published

Journal Article

Apoptotic signaling defects both promote tumorigenesis and confound chemotherapy. Typically, chemotherapeutics stimulate cytochrome c release to the cytoplasm, thereby activating the apoptosome. Although cancer cells can be refractory to cytochrome c release, many malignant cells also exhibit defects in cytochrome c-induced apoptosome activation, further promoting chemotherapeutic resistance. We have found that breast cancer cells display an unusual sensitivity to cytochrome c-induced apoptosis when compared with their normal counterparts. This sensitivity, not observed in other cancers, resulted from enhanced recruitment of caspase-9 to the Apaf-1 caspase recruitment domain. Augmented caspase activation was mediated by PHAPI, which is overexpressed in breast cancers. Furthermore, cytochrome c microinjection into mammary epithelial cells preferentially killed malignant cells, suggesting that this phenomenon might be exploited for chemotherapeutic purposes.

Full Text

Duke Authors

Cited Authors

  • Schafer, ZT; Parrish, AB; Wright, KM; Margolis, SS; Marks, JR; Deshmukh, M; Kornbluth, S

Published Date

  • February 15, 2006

Published In

Volume / Issue

  • 66 / 4

Start / End Page

  • 2210 - 2218

PubMed ID

  • 16489023

Pubmed Central ID

  • 16489023

International Standard Serial Number (ISSN)

  • 0008-5472

Digital Object Identifier (DOI)

  • 10.1158/0008-5472.CAN-05-3923

Language

  • eng

Conference Location

  • United States