Modulation of estrogen receptor alpha protein level and survival function by DBC-1.

Modulation of estrogen receptor alpha protein level and survival function by DBC-1. Research Abstract Details 

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Modulation of estrogen receptor alpha protein level and survival function by DBC-1. Abstract Text:

Amy M Trauernicht,Se Jin Kim,Nam Hee Kim,Thomas G Boyer,Amy M Trauernicht,Se Jin Kim,Nam Hee Kim,Thomas G Boyer,

Acquired resistance to endocrine therapy represents a major clinical obstacle to the successful management of estrogen-dependent breast cancers expressing estrogen receptor alpha (ERalpha). Because a switch from ligand-dependent to ligand-independent activation of ERalpha-regulated breast cancer cell growth and survival may define a path to endocrine resistance, enhanced mechanistic insight concerning the ligand-independent fate and function of ERalpha, including a more complete inventory of its ligand-independent cofactors, could identify novel markers of endocrine resistance and possible targets for therapeutic intervention in breast cancer. Here, we identify the deleted in breast cancer 1 gene product DBC-1 (KIAA1967) to be a principal determinant of unliganded ERalpha expression and survival function in human breast cancer cells. The DBC-1 amino terminus binds directly to the ERalpha hormone-binding domain both in vitro and in vivo in a strict ligand-independent manner. Furthermore, like estrogen, the antiestrogens tamoxifen and ICI 182,780 (7alpha,17beta-[9-[(4,4,5,5,5-pentafluoropentyl)sulfinyl]nonyl]estra-1,3,5(10)-triene-3,17-diol) disrupt the DBC-1/ERalpha interaction, thus revealing the DBC-1/ERalpha interface to be a heretofore-unrecognized target of endocrine compounds commonly used in hormonal therapy. Notably, RNA interference-mediated DBC-1 depletion reduces the steady-state level of unliganded but not liganded ERalpha protein, suggesting that DBC-1 may stabilize unliganded ERalpha by virtue of their direct association. Finally, DBC-1 depletion promotes hormone-independent apoptosis of ERalpha-positive, but not ERalpha-negative, breast cancer cells in a manner reversible by endocrine agents that disrupt the DBC-1/ERalpha interaction. Collectively, these findings establish a principal biological function for DBC-1 in the modulation of ERalpha expression and hormone-independent breast cancer cell survival.

Modulation of estrogen receptor alpha protein level and survival function by DBC-1. Publishing Authors By Initials

AM Trauernicht,SJ Kim,NH Kim,TG Boyer,AM Trauernicht,SJ Kim,NH Kim,TG Boyer,

For similar proteins: neoplasm proteins: tumor suppressor proteins research abstracts see: proteins: neoplasm proteins: tumor suppressor proteins research

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Modulation of estrogen receptor alpha protein level and survival function by DBC-1. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Molecular endocrinology (Baltimore, Md.)

VOLUME: 21

Page Numbers: 1526-36

Journal Abbreviation: Mol. Endocrinol.

ISSN: 0888-8809

DAY: 1

MONTH: 05

YEAR: 2007

Modulation of estrogen receptor alpha protein level and survival function by DBC-1. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8801431

Modulation of estrogen receptor alpha protein level and survival function by DBC-1. Keywords Mesh Terms:

KEYWORDS: Tumor Suppressor Proteins

MESH TERMS: metabolism

Chemical & Substance for Abstract: Modulation of estrogen receptor alpha protein level and survival function by DBC-1. Information

Substance Name: Tumor Suppressor Proteins

Registry Number: 0

Grant and Affiliation Information for Modulation of estrogen receptor alpha protein level and survival function by DBC-1.

AFFILIATION: Department of Molecular Medicine and Institute of Biotechnology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78245-3207, USA.

Country: United States

AGENCY: United States NCI

GRANT: CA098301-01

ACRONYM: CA

MEDLINETA: Mol Endocrinol

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