Expression of Human Estrogen Receptor and Studies of Estrogen-Mediated Transcription and Apoptosis

Zhang, Chengcheng

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Description

Title

Expression of Human Estrogen Receptor and Studies of Estrogen-Mediated Transcription and Apoptosis

Author(s)

Zhang, Chengcheng

Issue Date

1999

Doctoral Committee Chair(s)

Shapiro, David J.

Department of Study

Biochemistry

Discipline

Biochemistry

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

Biology, Microbiology

Language

eng

Abstract

E2 and the antiestrogen OHT, each induce apoptosis in stably transfected hER positive HeLa-ER5 cells. Using transient transfections and a reporter system to measure p38 activity, we show that E2 induces the p38 activity 12--36 fold in several ER positive cell lines, while OHT induces p38 activity 2--5 fold. A selective inhibitor of p38 MAP kinase, S13 203580, partially protects HeLa-ER5 cells against apoptosis induced by E2 or by OHT. We selected ER positive cell lines resistant to E2 or OHT-induced apoptosis and found that E2 and OHT use different pathways to activate p38. In ER positive MCF-7, human breast cancer cells, whose growth is stimulated by estrogen, E2 did not induce p38 or apoptosis, while OHT induced both the p38 pathway and apoptosis, and S13 203580 protected against OHT-induced apoptosis. This work provides the first evidence that estrogen and ant-estrogen activate the p38 signal transduction pathway, and links activation of the p38 pathway to apoptosis induced by estradiol or by OHT.

Graduation Semester

1999

Type of Resource

text

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