Faculty Articles
Evaluation of lipophilins as determinants of tumor cell response to estramustine.
Publication Title
The Journal of pharmacology and experimental therapeutics
Publisher
American Society for Pharmacology and Experimental Therapeutics
ISSN
0022-3565
Publication Date
12-1-2005
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
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.
DOI
10.1124/jpet.105.090860
Volume
315
Issue
3
First Page
1158
Last Page
1162
Disciplines
Medical Specialties | Medicine and Health Sciences | Osteopathic Medicine and Osteopathy
NSUWorks Citation
Tucker, Jody M; Lipatova, Zhanna; Beljanski, Vladimir; Townsend, Danyelle M; and Tew, Kenneth D, "Evaluation of lipophilins as determinants of tumor cell response to estramustine." (2005). Faculty Articles. 1557.
https://nsuworks.nova.edu/hpd_com_faculty_articles/1557
