ABSTRACT
Gender difference in the incidence of colorectal cancer is well known and has been supported by various epidemiologic studies. In Korea, women have lower incidence of colorectal cancer and adenoma, and the incidence in men has recently increased. Hormone replacement therapy in menopausal women is preventive of colorectal cancer but can cause cardiovascular diseases and breast cancer. Estrogen exerts diverse effects through estrogen receptors, ERalpha and ERbeta. ERbeta is associated with anti-proliferation and apoptosis. The ratio of ERalpha/ERbeta is important in the protection and tumorigenesis of colorectal cancer. Therefore ERbeta modulation has been investigated for preventing or treating colorectal cancer and avoiding adverse effects of estrogen at the same time. In addition, the gender-difference in the incidence of colorectal cancer should be taken into account when making guidelines on colorectal surveillance for Korean population.
Subject(s)
Humans , Adenoma/diagnosis , Colorectal Neoplasms/diagnosis , Estradiol Dehydrogenases/metabolism , Estrogen Receptor alpha/metabolism , Estrogen Receptor beta/metabolism , Estrogens/metabolism , Sex FactorsABSTRACT
<p><b>OBJECTIVE</b>To screen the proteins interacting with FXR1P for functional investigation of FXR1P.</p><p><b>METHODS</b>The yeast strain AH109 transformed with the recombinant expression vector pGBKT7/FXR1 was mated with the yeast strain Y187 pretransformed with human fetal brain cDNA library. The positive clones were screened and identified by sequence analysis.</p><p><b>RESULTS</b>The recombinant expression vector pGBKT7/FXR1 was constructed successfully. Five proteins binding to FXR1P were screened from human fetal brain cDNA library using the yeast two-hybrid system, including CMAS, FTH1, GOLGA4, HSD17B1 and CSH1.</p><p><b>CONCLUSIONS</b>These results provide new clues for investigating the biological functions of FXR1P and the pathogenesis of Fragile X syndrome.</p>
Subject(s)
Humans , Autoantigens , Genetics , Metabolism , Estradiol Dehydrogenases , Genetics , Metabolism , Ferritins , Genetics , Metabolism , Gene Library , Membrane Proteins , Genetics , Metabolism , Protein Binding , Protein Interaction Domains and Motifs , Genetics , RNA-Binding Proteins , Genetics , Metabolism , Two-Hybrid System TechniquesABSTRACT
<p><b>OBJECTIVE</b>To explore the relationship between the polymorphism of estrogen-biosynthesis genes (CYP17, CYP19, HSD17beta1) and risk of breast cancer.</p><p><b>METHODS</b>A matched case-control study was designed. From May 2007 to July 2008, 200 pairs of subjects with and without breast cancer were enrolled, who were matched by age and menstruation status. Demographical characteristics, dietary factors and reproductive factors were investigated by questionnaire. CYP17 locus 1931 (T-->C), CYP19 codon 264 (Arg-->Cys) and HSD17beta1 locus 1954 (A-->G) were identified by AS-PCR (allele-specific PCR). The gene-gene interaction were analyzed with the MDR model (multifactor dimensionality reduction). Based on the results of MDR model, an unconditional logistic regression model was simulated to estimate the ORs of interaction factors and other risk factors.</p><p><b>RESULTS</b>The main effect of CYP17, CYP19 and HSD17beta1 susceptible genotypes were not correlated to breast cancer (OR approximately 1, P > 0.05). The positive interaction effect between CYP17 (T 1931C) and HSD17beta1 (A1954G) was discovered by MDR model with a statistically significant difference (Sign test, P = 0.05). The model's testing balance accuracy was 56.00%, and crossing validation consistency was 10/10. Multivariable unconditional logistic regression showed that after adjusting BMI, intake of estrogen, age of first birth, number of abortion and period of breast feeding, the interaction item of CYP17 (T1931C) and HSD17beta1 (A1954G) was strongly and positively correlated to breast cancer (OR = 2.52, 95%CI = 1.54 to 4.11).</p><p><b>CONCLUSION</b>The estrogen-biosynthesis genes CYP17 (T1931C) and HSD17beta1 (A1954G) polymorphism may jointly increase the risk of breast cancer.</p>
Subject(s)
Female , Humans , Aromatase , Genetics , Breast Neoplasms , Genetics , Pathology , Carcinoma, Ductal, Breast , Genetics , Pathology , Case-Control Studies , Estradiol Dehydrogenases , Genetics , Gene Frequency , Genetic Predisposition to Disease , Genotype , Logistic Models , Polymorphism, Single Nucleotide , Risk Factors , Steroid 17-alpha-Hydroxylase , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To explore the mechanism of inhibitory effect of SLW on estrogen production by endometrial cells of endometriosis.</p><p><b>METHOD</b>After the model of eutopic primary cultured endometrial cells of endometiosis and hysteromyoma in vitro was successfully established, the changes of steroidgenic factor-1 (SF-1), chicken ovalbumin upstream-transcription factor (COUP-TF), 17-beta-hydroxysteroid dehydrogenase 1 (17-beta-HSD1) and 17-beta-hydroxysteroid dehydrogenase 2 (17-beta-HSD2) mRNA were detected by RT-PCR before and after treatment of medicated serum of SLW. The changes of SF-1 and COUP-TF protein were also observed by western blot synchronously according to the same treatment method mentioned-above. Meanwhile ,the data of hysteromyoma group was obtained from the above experiments.</p><p><b>RESULT</b>The expression of SF-1 mRNA and protein, 17-beta-HSD1 mRNA was weak, but COUP-TF mRNA and protein, 17-beta-HSD2 mRNA was remarkable in Hysteromyoma endometrium, as compared with those of endometiosis ,which was taken as control group (P<0.01). After the 48 hours' treatment of medicated serum of 5.0, 2.5 g kg(-1) d(-1) of SLW , the expression of COUP-TF mRNA and protein, 17beta-HSD2 mRNA was found significantly increased, but SF-1 mRNA and protein, 17-beta-HSD 1 mRNA was decreased in contrast to the control group (P <0.01 or P <0.05). Although the expresson of COUP-TF mRNA and protein was increased, SF-1 protein and 17-beta-HSD1 mRNA was decreased in 1.25 g kg(-1) d(-1) medicated serum group ,compared with those of the control group (P <0.01), the low dose group had no apparent inhibitory effect on the expression of SF-1, 17-beta-HSD2 mRNA.</p><p><b>CONCLUSION</b>The medicated serum of SLW could inhibit the secretion of estradiol in eutopic endometrial cells of endometiosis, and its mechanism might be associated with combined action of inhibiting expression of SF-1, 17-beta-HSD1 and up-regulating expression of COUP-TF, 17-beta-HSD2.</p>
Subject(s)
Adult , Animals , Female , Humans , Middle Aged , Rats , 17-Hydroxysteroid Dehydrogenases , Genetics , COUP Transcription Factors , Genetics , Drugs, Chinese Herbal , Pharmacology , Endometriosis , Blood , Metabolism , Pathology , Endometrium , Metabolism , Pathology , Estradiol Dehydrogenases , Estrogens , Gene Expression Regulation , In Vitro Techniques , RNA, Messenger , Genetics , Metabolism , Serum , Chemistry , Steroidogenic Factor 1 , GeneticsABSTRACT
Biotransformation of estradiol (E2) and estrone (E1) and the concentrations of NAD, NADPH and 17 beta-estradiol dehydrogenase (E2DH) were measured in the uterus of rabbits treated with tamoxifen (Tam) in two doses; 100 micrograms/day, (Tam 100) and 500 micrograms/day, (Tam 500), E2 (10 micrograms/day) and combination of E2 + Tam 500 for 4 days. The concentration of NAD in Tam 500 treated group was significantly higher than E2, low dose Tam and E2 + Tam 500 treated groups (P < 0.01). The concentration of NAD in E2+ Tam 500 uteri was also significantly higher than E2 treated uteri. The concentration of NADPH was not significantly different from each other amongst the various treatment groups. The studies have shown that E2DH in E2 treated uteri was less than control and Tam 500 treated groups. A significant rise in the enzyme estradiol oxidoreductase (E2OR) activity (P < 0.02) was observed in E2 + Tam 500 treated uteri over control and other treated groups whereas high dose Tam decreased the E2OR activity significantly over the E2 treated group. The rate of conversion of E1 to E2 in Tam 500 treated group was significantly less than the other treatment groups except E2 + Tam 500 treated group (P < 0.04). This study showed that E2 decreases the uterine biosynthesis of NAD and E2DH and the biotransformation of E2 to E1, while high dose Tam increases uterine NAD, E2DH activity and E2 to E1 conversion.