Accession Number:

ADB281633

Title:

Regulation of Growth and Metastases in an Estrogen Independent Breast Cancer Cell by Vitamin D Compounds

Descriptive Note:

Annual rept. 1 Aug 1999-30 Jul 2001

Corporate Author:

NOTRE DAME UNIV IN

Personal Author(s):

Report Date:

2001-08-01

Pagination or Media Count:

49.0

Abstract:

Metastatic spread of cancer continues to be the greatest barrier to cancer cure. In ER-positive breast cancer cells, the effects of 1,25 OH 2D3 are similar to those induced by anti-estrogens, where l,25OH2D3 transcriptionally down-regulates ER expression. If so, then sensitivity to l,25OH2D3 mediated apoptosis could be reduced in estrogen independent breast cancer cells. We focused on the role of vitamin D3 compounds to activate the apoptotic pathway in ER-negative SUM-l59PT cells and tumors and whether vitamin D compounds were capable of inhibiting the invasion of SUM-l59PT cells. Our major findings are that 1,25 OH 2D3 induces apoptosis in the ER-negative SUM-l59PT cells by disruption of mitochondrial function which is associated with Bax trans location to mitochondria and cytochrome c release. Downstream events of the mitochondria included PARPpolyADP-ribose polymerase cleavage. Our in vivo data is the first to show apoptotic tumor regression of an ER- independent breast cancer model system by the vitamin D analogue EBl089. Our in vitro invasion as says demonstrate a dramatic reduction in invasive potential of SUM-l59PT cells upon exposure to 1,25 OH 2D3 and EBl089 and we are currently testing the effects of EBl089 on metastatic spread in vivo. Utilizing our SUM-l59PTGFPP model system in vivo we can more efficiently examine the mechanisms of invasion and metastasis and the efficacy of vitamin D compounds to modulate these processes.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE