17 beta-Hydroxysteroid dehydrogenases (17HSDs) regulate the biological activity of
sex steroid hormones in a variety of tissues by catalyzing the interconversions between highly active
steroid hormones, e.g.
estradiol and
testosterone, and corresponding less active
hormones,
estrone and
androstenedione. Epidemiological and endocrine evidence indicates that
estrogens play a role in the etiology of
breast cancer, while
androgens are involved in mechanisms controlling the growth of normal and malignant prostatic cells. Using LNCaP
prostate cancer cell lines, we have developed a cell model to study the progression of
prostate cancer. In the model LNCaP cells are transformed in culture condition into more aggressive cells. Our data suggest that substantial changes in
androgen and
estrogen metabolism occur in the cells, leading to increased production of active
estrogens during the process. In
breast cancer, the reductive 17HSD type 1 activity is predominant in malignant cells, while the oxidative 17HSD type 2 mainly seems to be present in non-malignant breast epithelial cells. Deprivation of an
estrogen response by using specific 17HSD type 1 inhibitors is a tempting approach in treating
estrogen-dependent
breast cancer. Our recent studies demonstrate that in addition to
sex hormone target tissues,
estrogens may be important in the development of
cancer in some other tissues previously not considered to be
estrogen target tissues, such as the gastrointestinal tract.