Androgen-independent prostate cancer cells acquire the complete steroidogenic potential of synthesizing testosterone from cholesterol

Paulette R. Dillard, Ming-Fong Lin, Shafiq A. Khan

Research output: Contribution to journalArticle

144 Citations (Scopus)

Abstract

The proliferation and differentiation of normal prostate epithelial cells depends upon the action of androgens produced by the testis. Prostate cancers retain the ability to respond to androgens in the initial stages of cancer development, but progressively become independent of exogenous androgens in advanced stages of the disease while maintaining the expression of functional androgen receptor (AR). In the present study, we have determined the potential of prostate cancer cells to synthesize androgens from cholesterol which may be involved in intracrine regulation of AR in advanced stages of the disease. Established androgen-independent prostate cancer cell lines, PC3 and DU145 cells, expressed mRNA and proteins for scavenger receptor type B1 (SRB1), steroidogenic acute regulatory (StAR) protein, cytochrome P450 cholesterol side chain cleavage (P450scc), 3β-hydroxysteroid dehydrogenase (3β-HSD) and other enzymes involved in androgen biosynthesis. Expression of all these proteins and enzymes was significantly higher in the androgen-independent derivative of LNCaP prostate cancer cells (C81) than in the androgen-dependent cell line (C33). In serum-free cultures, the androgen-independent C81 cells secreted ∼5-fold higher testosterone than C33 cells as determined in the conditioned media by immunoassays. These cells could also directly convert radioactive cholesterol into testosterone which was identified by thin layer chromatography. These results for the first time show that prostate cancer cells in advanced stages of the disease could synthesize androgens from cholesterol and hence are not dependent upon testicular and/or adrenal androgens.

Original languageEnglish (US)
Pages (from-to)115-120
Number of pages6
JournalMolecular and Cellular Endocrinology
Volume295
Issue number1-2
DOIs
StatePublished - Nov 25 2008

Fingerprint

Androgens
Testosterone
Prostatic Neoplasms
Cholesterol
Cells
Androgen Receptors
3-Hydroxysteroid Dehydrogenases
Scavenger Receptors
Cell Line
Thin layer chromatography
Biosynthesis
Enzymes
Conditioned Culture Medium
Thin Layer Chromatography
Immunoassay
Cell culture
Cytochrome P-450 Enzyme System
Testis
Prostate
Proteins

Keywords

  • Androgen biosynthesis
  • Androgen receptor
  • Androgen-independence
  • Intracrine regulation
  • Prostate cancer
  • Steroidogenesis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

Cite this

Androgen-independent prostate cancer cells acquire the complete steroidogenic potential of synthesizing testosterone from cholesterol. / Dillard, Paulette R.; Lin, Ming-Fong; Khan, Shafiq A.

In: Molecular and Cellular Endocrinology, Vol. 295, No. 1-2, 25.11.2008, p. 115-120.

Research output: Contribution to journalArticle

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