17 Beta-hydroxysteroid dehydrogenase in human breast cancer: analysis of kinetic and clinical parameters.
In this study, we assessed the rate of estradiol degradation via the 17 beta-hydroxysteroid dehydrogenase (HSD) enzyme in breast tumors from postmenopausal women. We initially studied the effects of time, level of enzyme activity, amount of tissue assayed, and substrate concentration on the linearity of conversion of estradiol to estrone in breast tumor homogenates. The reaction was demonstrated to be linear when less than 15% conversion of estradiol to estrone occurred over 30 min with homogenates produced from 2.5 mg of tissue. Detailed kinetic experiments demonstrated the presence of two classes of enzyme activity, one with high affinity and the other with low affinity. In 83% of the tumors examined, the high affinity form was present and had a median Km of 0.62 microM and Vmax of 82 nmol/g protein/h. In 29 tumors, HSD activity could be precisely quantified and correlated with clinical parameters. No statistically significant correlation of enzyme activity with estrogen receptor (r2 = 0.06) or progesterone receptor (r2 = 0.006) or with patient age could be detected (r2 = 0.001). In 12 additional tumors, activity exceeded 15% conversion of estradiol to estrone at 30 min and precise quantitation was not possible. The average content of progesterone receptor was similar for these 12 tumors as for the 19 with lower HSD activity. However, estrogen receptor content and patient age were lower in the group with high HSD activity. The finding of a high affinity form of HSD in this study provides support for the biological importance of this enzyme in breast cancer tissues.
Leszczynski
D
D
Department of Medicine, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.
Santner
S J
SJ
Feil
P D
PD
Santen
R J
RJ
D015067:17-Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D001943:Breast Neoplasms / Q000201:enzymology*; D004958:Estradiol / Q000096:biosynthesis; D004970:Estrone / Q000096:biosynthesis; D006801:Humans; D007700:Kinetics
D004970:Estrone; D004958:Estradiol; D015067:17-Hydroxysteroid Dehydrogenases; C032690:3-alpha-(17-beta)-hydroxysteroid dehydrogenase (NAD(+))