17 beta-hydroxysteroid dehydrogenases and cancers.
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.
Vihko
P
P
Biocenter Oulu and Research Center for Molecular Endocrinology, University of Oulu, P.O. Box 5000, FIN-90014 Oulu, Finland. pvihko@whoccr.oulu.fi
Härkönen
P
P
Oduwole
O
O
Törn
S
S
Kurkela
R
R
Porvari
K
K
Pulkka
A
A
Isomaa
V
V
D015067:17-Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D001943:Breast Neoplasms / Q000201:enzymology; D002460:Cell Line; D003110:Colonic Neoplasms / Q000201:enzymology / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000201:enzymology*; D010100:Oxygen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000201:enzymology; D020033:Protein Isoforms; D014407:Tumor Cells, Cultured
D020033:Protein Isoforms; D015067:17-Hydroxysteroid Dehydrogenases; D010100:Oxygen