17 beta-Hydroxysteroid dehydrogenases (17HSDs) catalyze the interconversions between active 17 beta-
hydroxysteroids and less-active
17-ketosteroids thereby affecting the availability of biologically active
estrogens and
androgens in a variety of tissues. The
enzymes have different enzymatic properties and characteristic cell-specific expression patterns, suggesting differential physiological functions for the
enzymes. Epidemiological and endocrine evidence indicate that
estrogens play a key role in the etiology of
breast cancer while
androgens are involved in mechanisms controlling the growth of prostatic cells, both normal and malignant. Recently, we have developed, using LNCaP
prostate cancer cell lines, a cell model to study the progression of
prostate cancer. In the model LNCaP cells are transformed in culture condition to more aggressive cells, able to grow in
suspension cultures. Our results suggest that substantial changes in
androgen and
estrogen metabolism occur in the cells during the process. These changes lead to increased production of active
estrogens during transformation of the cells. Data from studies of breast cell lines and tissues suggest that the oxidative 17HSD type 2 may predominate in human non-malignant breast epithelial cells, while the reductive 17HSD type 1 activity prevails in malignant cells. Deprivation of an
estrogen response by using specific 17HSD type 1 inhibitors is a tempting approach to treat
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 as
estrogen target tissues such as colon. Our data show that the abundant expression of 17HSD type 2 present in normal colonic mucosa is significantly decreased during
colon cancer development.