17beta-HSD1 is highly expressed in breast and ovary tissues and represents a prognostic marker for the tumor progression and survival of patients with breast cancer and other estrogen-dependent tumors
a high HSD17B1 to HSD17B2 ratio, as well as high HSD17B1 on its own is associated with worse prognosis and increased risk of recurrence in patients with ERalpha-positive tumors. An increased copy number of the HSD17B1 gene is correlated with decreased breast cancer survival
the mouse monoclonal antibody for AKR1C3, 10B10, is highly specific and sensitive for detecting AKR1C3 expression including patient samples. The proper detection of AKR1C3 expression is critical for therapeutics targeting AKR1C3, 10B10 will be a valuable tool in clinic for AKR1C3 precision therapy. 10B10 is specific to AKR1C3 protein and has a very low cross-activity against other AKR1 proteins
binding of equilin at the active site of the enzyme is the basis for inhibition of reduction of estrone to estradiol. One possible outcome of estrogen replacement therapy in vivo can be the reduction of estradiol levels in breast tissues and hence the reduced risk of estrogen-dependent breast cancer
as estradiol stimulates the growth and development of hormone-dependent breast cancer, inhibition of the final step of its synthesis is an attractive target for the treatment of this disease
estrogenic response for estrone is enhanced by the local action of HSD17B1 in vivo. Thus the enzyme is a potential target for pharmacological inhibition of estrogen activation. Targeted inhibition of HSD17B1 is a promising therapeutic approach to modulate estrogen response in the target tissue with less severe side effects as compared with antiestrogens
type 1 17beta-hydroxysteroid dehydrogenase is an interesting biological target for designing drugs for the treatment of estrogen-sensitive diseases such as breast cancer
disease iondications for HSD17B1 inhibitors in disorders in the female reproductive organs associated with enhanced androgen action, such as ovarian serous cystadenomas
17beta-hydroxysteroid dehydrogenase type 2 is mainly involved in the conversion of estradiol into estrone. Their ratio is decreased from 9/1 to 7/3 after over-expression of 17beta-hydroxysteroid dehydrogenase type 2 in MCF-7 cells already over-expressing 17beta-hydroxysteroid dehydrogenase type 1. The ratio is further decreased by the addition of the oxidative cofactor, NAD, to the cell culture to facilitate the estradiol to estrone conversion catalyzed by 17beta-hydroxysteroid dehydrogenase type 2
application of medroxyprogestrone acetate, dydrogesterone and dienogest significantly decreases isoforms HSD17B1 and CYP19A1 expression and significantly increases isoform HSD17B2 expression. Dydrogesterone and dienogest also significantly suppress estrogen receptors ESR1 and ESR2 transcription, whereas medroxyprogestrone acetate and dydrogesterone significantly reduce mRNA levels of G protein-coupled estrogen receptor 1. Results thus suggest that in peritoneal endometriosis the beneficial effects of these progestins can be explained by lower HSD17B1 and higher HSD17B2 mRNA and protein levels, which lead to reduced local estradiol biosynthesis
isoform 17betaHSD6 is expressed in estrogen receptor beta-positive epithelial cells of the human prostate. In prostate cancers of Gleason grade higher than 3, both estrogen receptor beta and isoform 17betaHSD6 are undetectable
Patients with oestrogen positive tumours with high isoform 17betaHSD14 expression have fewer local recurrences when treated with tamoxifen compared to patients with lower tumoural 17betaHSD14 expression, for whom tamoxifen does not reduce the number of local recurrences. No prognostic importance of 17betaHSD14 is seen for systemically untreated patients
twenty four hours after addition of different concentrations of estrone and estradiol, the ratio stabilizes to around 9/1 in breast cancer cell lines with high expression of 17beta-hydroxysteroid dehydrogenase type 1, such as T47D, BT 20, and JEG 3 cells, whereas it approaches 1/5 in cells with low expression of 17beta-hydroxysteroid dehydrogenase type 1, such as MCF-7 cells. The estradiol/estrone concentration ratio is modified to 9/1 in MCF-7 and HEK-293 cells over-expressing 17beta-hydroxysteroid dehydrogenase type 1. In T47D and BT 20 cells , this ratio is decreased from 9/1 to nearly 1/5 after 17beta-hydroxysteroid dehydrogenase type 1 knockdown by specific siRNAs
17betaHSD1 is an important prognostic factor in non-small cell lung carcinoma, NSCLC, patients and targeting 17betaHSD1 activity may further improve the clinical response in estrogen responsive NSCLC patients
enzyme inhibition can lead to desired increase of estradiol and testosterone levels in the bone tissue and may be used for the treatment of osteoporosis
inhibition of 17beta-hydroxysteroid dehydrogenase type 2 (17beta-HSD2) can help maintaining the appropriate bone mass density in osteoporosis by increasing the level of estradiol and testosterone in bone