Identification of cyclin D1- and estrogen-regulated genes contributing to breast carcinogenesis and progression.

Identification of cyclin D1- and estrogen-regulated genes contributing to breast carcinogenesis and progression. Research Abstract Details 

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Identification of cyclin D1- and estrogen-regulated genes contributing to breast carcinogenesis and progression. Abstract Text:

Chuanwei Yang,Sally Trent,Viviana Ionescu-Tiba,Lan Lan,Toshi Shioda,Dennis Sgroi,Emmett V Schmidt,

Tumors can become lethal when they progress from preinvasive lesions to invasive carcinomas. Here, we identify candidate tumor progression genes using gene array analysis of preinvasive and invasive tumors from mice, which were then evaluated in human cancers. Immediate early response protein IEX-1, small stress protein 1 (HSPB8), and tumor necrosis factor-associated factor-interacting protein mRNAs displayed higher expression levels in invasive lesions than in preinvasive lesions using samples obtained by laser capture microdissection (LCM) from transgenic erbB2, ras, and cyclin D1 mice. LCM-isolated tissues from patient-matched normal, ductal carcinoma in situ, and invasive ductal carcinoma revealed similar increased expression in invasive human cancers compared with preinvasive and normal samples. These genes induced anchorage independence, increased cell proliferation, and protected against apoptosis, singly or in collaboration with erbB2. Surprisingly, they were all up-regulated by 17beta-estradiol and cyclin D1, and cyclin D1 overexpression increased p300/CBP binding to their promoters, supporting the model that cyclin D1-estrogen receptor (ER) coactivator interactions may be important to its role in ER-positive breast cancer. Additionally, an irreversible dual kinase inhibitor of ErbB signaling inhibited expression of the same genes. The up-regulation of genes contributing to increased invasiveness of ER-positive cancers offers a novel explanation for the contribution of cyclin D1 to a worse prognosis in ER-positive cancers. As targets of estrogen, cyclin D1, and erbB2 signaling, these candidates offer insights into the nature of the second events involved in breast cancer progression, regulatory events contributing to invasion, and potential targets of combined inhibition of hormone and growth factor signaling pathways.

Identification of cyclin D1- and estrogen-regulated genes contributing to breast carcinogenesis and progression. Publishing Authors By Initials

C Yang,S Trent,V Ionescu-Tiba,L Lan,T Shioda,D Sgroi,EV Schmidt,

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Identification of cyclin D1- and estrogen-regulated genes contributing to breast carcinogenesis and progression. Journal Published:

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

Journal: Cancer research

VOLUME: 66

Page Numbers: 11649-58

Journal Abbreviation: Cancer Res.

ISSN: 0008-5472

DAY: 15

MONTH: Dec

YEAR: 2006

Identification of cyclin D1- and estrogen-regulated genes contributing to breast carcinogenesis and progression. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2984705

Identification of cyclin D1- and estrogen-regulated genes contributing to breast carcinogenesis and progression. Keywords Mesh Terms:

KEYWORDS: Reference Values

MESH TERMS: genetics

Chemical & Substance for Abstract: Identification of cyclin D1- and estrogen-regulated genes contributing to breast carcinogenesis and progression. Information

Substance Name: Cyclin D1

Registry Number: 136601-57-5

Grant and Affiliation Information for Identification of cyclin D1- and estrogen-regulated genes contributing to breast carcinogenesis and progression.

AFFILIATION: Massachusetts General Hospital Cancer Research Center, Massachusetts General Hospital Cancer Center--Harvard University, 55 Fruit Street, GRJ 904, Boston, MA 02114, USA.

Country: United States

AGENCY: United States NCI

GRANT: R01 CA69069

ACRONYM: CA

MEDLINETA: Cancer Res

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