Androgens regulate cell proliferation of human prostate cancer in culture by up-regulating an autocrine growth loop involving EGF receptor and its ligand TGFalpha

Update item information
Publication Type dissertation
School or College College of Social & Behavioral Science
Department Psychology
Author Liu, Xin-Hua
Title Androgens regulate cell proliferation of human prostate cancer in culture by up-regulating an autocrine growth loop involving EGF receptor and its ligand TGFalpha
Date 1992-12
Description Androgens affect growth and functional integrity of the prostate gland, and many prostate cancers retain dependency on androgens for growth. The transforming growth factor (TGF)-ce binds to the epidermal growth factor (EGF) receptor and is an autocrine growth factor, which could mediate the mitogenic effect of steroid hormones. To test this hypothesis, we examined the effects of 5a-dihydrotestosterone (DHT) and testosterone on cell proliferation, regulation of TGF-a and EGF receptor mRNA levels and EGF receptor content in an androgen-sensitive human prostate cancer cell line (ALVA 101). ALVA 101 cells cultured in serum-free medium without androgen expressed a TGF-a mRNA transcript of 4.8 kb and an EGF receptor mRNA transcript of 10 kb. After 24 h treatment with DHT (108M) or testosterone (10~8M), TGF-a mRNA levels increased 3-and 2.5-fold, respectively, and EGF receptor mRNA levels 2- and 1.5-fold, respectively. The mitogenic effects of androgens and EGF or TGF-a on the proliferation of ALVA 101 cells were then examined. In serum-free medium, cell numbers increased at day 5 in response to 10-8M DHT (18%, p<0.01), 10-8M testosterone (15%, p<0.01), 20 ng/ml EGF (16%, p<0.01) and 50 ng/ml TGF-a (34%, p<0.01). In addition, DHT combined with TGF-a or testosterone combined with EGF increased cell number 43% and 40% above control, respectively. (p<0.01 vs. DHT, p<0.05 vs. TGF-a, testosterone or EGF alone). Further, 3H-thymidine incorporation studies confirmed the mitogenic effects of androgens and TGF-a or EGF on ALVAlOl cells. The anti-EGF receptor antibody (528) blocked the cell proliferation induced by either DHT or TGF-a. We conclude that DHT and testosterone stimulate synthesis of TGF-a and EGF receptor mRNAs and EGF receptor content in ALVAlOl cells, and that DHT and testosterone may enhance ALVAlOl cell proliferation through an autocrine mechanism involving TGF-a and the EGF/TGF-a receptor.""
Type Text
Publisher University of Utah
Subject Epidermal Growth
Subject MESH Androgens; Prostatic Neoplasms; Transforming Growth Factors
Dissertation Institution University of Utah
Dissertation Name PhD
Language eng
Relation is Version of Digital reproduction of "Androgens regulate cell proliferation of human prostate cancer in culture by up-regulating an autocrine growth loop involving EGF receptor and its ligand TGFalpha Spencer S. Eccles Health Sciences Library.
Rights Management © Xin-Hua Liu.
Format Medium application/pdf
Format Extent 1,383,914 bytes
Identifier undthes,4117
Source Original: University of Utah Spencer S. Eccles Health Sciences Library (no longer available)
Master File Extent 1,383,974 bytes
ARK ark:/87278/s6k35wf9
Setname ir_etd
Date Created 2012-04-24
Date Modified 2021-05-06
ID 190795
Reference URL https://collections.lib.utah.edu/ark:/87278/s6k35wf9
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