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Hormonal regulation of transforming growth factor beta-2 expression in human prostate cancer
C Knabbe1, H Klein, G Zugmaier
1Department of Clinical Chemistry, University Hospital Eppendorf, Hamburg, Germany.
Abstract:
We have previously shown that a transforming factor-beta species (TGF beta) is a hormonally regulated negative growth factor in estrogen responsive MCF-7 human breast cancer cells. We now demonstrate that androgen withdrawal leads to a significant stimulation of TGF beta-2 mRNA in the androgen-responsive human prostate carcinoma cell line LNCaP. These data indicate that TGF beta-2 is a marker of (anti)androgen action in human prostate cancer in vitro. Based on these results we addressed the question of whether TGF beta-2 represented a marker of (anti)androgen action in prostate cancer in vivo: expression of TGF beta mRNA was determined by RNAase protection analysis in normal and malignant prostate tissue obtained from 9 prostate carcinoma patients without endocrine therapy. In parallel, the nuclear dihydrotestosterone (DHT) concentration was measured as an indicator of androgen stimulation in the same tissues. The following results were obtained. Both normal and cancerous tissues show nuclear accumulation of DHT indicating a functional androgen receptor system. TGF beta-2 is equally expressed in both normal and cancerous tissue. Expression of TGF beta-2 and nuclear DHT concentrations are correlated in both benign and malignant tissue. We conclude that TGF beta-2 is a marker of (anti)hormonal action in androgen-dependent tissue.
Insights
Transforming growth factor-beta 2 (TGF beta-2) is stimulated by androgen withdrawal in prostate cancer cells. This suggests TGF beta-2 may serve as a marker for hormonal action in androgen-dependent tissues.
Area of Science:
- Oncology
- Endocrinology
- Molecular Biology
Background:
- Transforming growth factor-beta (TGF beta) acts as a hormonally regulated negative growth factor in breast cancer cells.
- Androgen withdrawal significantly stimulates TGF beta-2 mRNA in the LNCaP prostate cancer cell line.
- TGF beta-2 is proposed as a marker for (anti)androgen action in prostate cancer.
Purpose of the Study:
- To investigate if TGF beta-2 serves as a marker for (anti)androgen action in prostate cancer.
- To determine the expression of TGF beta mRNA in normal and malignant prostate tissue.
- To correlate TGF beta-2 expression with nuclear dihydrotestosterone (DHT) concentrations in vivo.
Main Methods:
- RNAase protection analysis to measure TGF beta mRNA expression.
- Measurement of nuclear dihydrotestosterone (DHT) concentration as an indicator of androgen stimulation.
- Analysis of prostate tissue from patients without endocrine therapy.
Main Results:
- Both normal and cancerous prostate tissues exhibit nuclear DHT accumulation, indicating functional androgen receptors.
- TGF beta-2 is expressed equally in both normal and cancerous prostate tissues.
- A correlation exists between TGF beta-2 expression and nuclear DHT concentrations in benign and malignant tissues.
Conclusions:
- TGF beta-2 is a marker of (anti)hormonal action in androgen-dependent tissues.
- The study provides in vitro and in vivo evidence for TGF beta-2's role as a hormonal marker.