Epidermal growth factor receptor-dependent stimulation of amphiregulin expression in androgen-stimulated human prostate cancer cells

Inder Sehgal, Jane Bailey, Karen Hitzemann, Mark R. Pittelkow, Nita Jane Maihle

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Amphiregulin is a heparin-binding epidermal growth factor (EGF)-related peptide that binds to the EGF receptor (EGF-R) with high affinity. In this study, we report a role for amphiregulin in androgen-stimulated regulation of prostate cancer cell growth. Androgen is known to enhance EGF-R expression in the androgen-sensitive LNCaP human prostate carcinoma cell line, and it has been suggested that androgenic stimuli may regulate proliferation, in part, through autocrine mechanisms involving the EGF-R. In this study, we demonstrate that LNCaP cells express amphiregulin mRNA and peptide and that this expression is elevated by androgenic stimulation. We also show that ligand-dependent EGF-R stimulation induces amphiregulin expression and that androgenic effects on amphiregulin synthesis are mediated through this EGF-R pathway. Parallel studies using the estrogen-responsive breast carcinoma cell line, MCF-7, suggest that regulation of amphiregulin by estrogen may also be mediated via an EGF-R pathway. In addition, heparin treatment of LNCaP cells inhibits androgen-stimulated cell growth further suggesting that amphiregulin can mediate androgen-stimulated LNCaP proliferation. Together, these results implicate an androgen-regulated autocrine loop composed of amphiregulin and its receptor in prostate cancer cell growth and suggest that the mechanism of steroid hormone regulation of amphiregulin synthesis may occur through androgen upregulation of the EGF-R and subsequent receptor-dependent pathways.

Original languageEnglish (US)
Pages (from-to)339-347
Number of pages9
JournalMolecular Biology of the Cell
Volume5
Issue number3
DOIs
StatePublished - Jan 1 1994

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Epidermal Growth Factor Receptor
Androgens
Prostatic Neoplasms
Epidermal Growth Factor
Heparin
Estrogens
Growth
Amphiregulin
Cell Line
Peptides
Prostate
Up-Regulation
Steroids
Hormones
Breast Neoplasms
Ligands
Carcinoma
Messenger RNA

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Epidermal growth factor receptor-dependent stimulation of amphiregulin expression in androgen-stimulated human prostate cancer cells. / Sehgal, Inder; Bailey, Jane; Hitzemann, Karen; Pittelkow, Mark R.; Maihle, Nita Jane.

In: Molecular Biology of the Cell, Vol. 5, No. 3, 01.01.1994, p. 339-347.

Research output: Contribution to journalArticle

Sehgal, Inder ; Bailey, Jane ; Hitzemann, Karen ; Pittelkow, Mark R. ; Maihle, Nita Jane. / Epidermal growth factor receptor-dependent stimulation of amphiregulin expression in androgen-stimulated human prostate cancer cells. In: Molecular Biology of the Cell. 1994 ; Vol. 5, No. 3. pp. 339-347.
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