Evaluation of lipophilins as determinants of tumor cell response to estramustine.

Abstract

Estramustine administered orally as estramustine phosphate (EMP) remains a major tool in hormone refractory prostate cancer chemotherapy. The presence of estramustine binding protein, prostatin, in prostate tissue may be a determinant of response to treatment. Lipophilins are secretory proteins with homology to prostatin. Reverse transcription-polymerase chain reaction was performed to estimate expression patterns of lipophilins A to C in human biopsies and cell lines resistant to estramustine. Although lipophilin A was not expressed in prostate tissue, both lipophilins B and C were expressed in normal and tumor prostate without significant differences. For lipophilin C, a somatic mutation (T to C transition at positions 409 and 412) was found in human tumor samples and absent in normal prostate tissue. No consistent response to EMP was observed in enhanced green fluorescent protein (EGFP)-tagged lipophilin C-transfected PC3 cells compared with parental controls. Among these EGFP-lipophilin C clones, no direct correlation between response to EMP treatment (IC50 values) and EGFP expression was observed (p = 0.73). Lipophilin C mRNA levels did not vary significantly between wild-type and estramustine-resistant cells in prostate (DU145 and PC3) and ovarian (SKOV3) cancer cell lines. Overall, these results suggest that lipophilins are not specific determinants of estramustine efficacy.

• Authors: Jody M Tucker, Zhanna Lipatova, Vladimir Beljanski, Danyelle M Townsend, Kenneth D Tew
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 315 Issue 3 Pg. 1158-62 (Dec 2005) ISSN: 0022-3565 [Print] United States
• PMID: 16120813 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antineoplastic Agents, Hormonal
• Neoplasm Proteins
• RNA, Messenger
• Recombinant Fusion Proteins
• Estramustine

Topics

• Antineoplastic Agents, Hormonal (pharmacology, therapeutic use)
• Biopsy
• Blotting, Western
• Cell Line, Tumor
• Cell Survival (drug effects)
• Clone Cells
• Estramustine (pharmacology, therapeutic use)
• Flow Cytometry
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Inhibitory Concentration 50
• Male
• Mutation
• Neoplasm Proteins (classification, drug effects, genetics, metabolism)
• Prostatic Neoplasms (drug therapy, genetics, metabolism)
• RNA, Messenger (metabolism)
• Recombinant Fusion Proteins (metabolism)