Faculty Articles

Title

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

ISBN or ISSN

0022-3565

Publication Title

The Journal of pharmacology and experimental therapeutics

Volume

315

Issue

3

Publication Date / Copyright Date

12-1-2005

First Page

1158

Last Page

1162

Publisher

American Society for Pharmacology and Experimental Therapeutics

DOI Number

10.1124/jpet.105.090860

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.

Disciplines

Medical Specialties | Medicine and Health Sciences | Osteopathic Medicine and Osteopathy

Keywords

Antineoplastic Agents, Hormonal, Biopsy, Blotting, Western, Cell Line, Tumor, Cell Survival, Clone Cells, Estramustine, Flow Cytometry, Gene Expression Regulation, Neoplastic, Humans, Inhibitory Concentration 50, Male, Mutation, Neoplasm Proteins, Prostatic Neoplasms, RNA, Messenger, Recombinant Fusion Proteins

Peer Reviewed

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