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

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.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Biochemistry

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2015

Author dc:creator

• Zhang, Chengcheng

Contributors dc:contributor

• Shapiro, David J.

• Biology, Microbiology

Language dc:language

eng

Identifier

(MiAaPQ)AAI9953184

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/84911