Expression Of Estrogen Receptor β And α In Human Breast And Their Significance In Hormone Replacement Therapy

Background Postmenopausal hormone rep1acement therapy (HRT) hasbeen applied to al1eviate menopausal symptoms and reduce the risk ofosteoporosis, coronary heart disease, A1zheimer's disease, andco1orecta1 cancer. However, the risk of breast cancer may be increasedafter long duration of HRT usage. It's valuab1e to deve1op a newtissue--selective HRT, Which can protect target organ, such as bone,brain, heart, and co1on, without stimulation to breast or endometrium.Estrogens act through estrogen receptor(ER). ER is a member of thenuclear receptor super family, a ligand--activated transcriptionfactor. It was considered that a single ER was responsib1e for a11of the biologica1 effects of estrogens, unti1 recently a nove1 ER,ERD, was cloned from rat, mouse and human, and thus the classica1ER was referred to as ER Q. ER Q and ER D exhibit simi1arligand--transduced transcriptiona1 activation, but differ in tissuedistribution, ligand binding affinity, and biological function.Estrogen p1ays an important role in the development of hunan breastcancer, and meantime, perturbations of ER signa1 transduction arethought to contribute to tumor progression and the eventualdeve1opment of a hormone--independent and more aggressive phenotype.It was assumed that the well--documented role of estrogen in breasttumorigenesis might also invo1ve both ER subtypes, and a1teredexpression of these two receptors might occur during breasttumorigenesis. But it's sti1l uncertain how ER D and ER Q change andcoactivate during breast tumorigenesis and tumor aggression. Theresearch of ERD and ERQ in human breast has been vacant in Chinaup to now.0bjective The objective of this research is to investigate thedifferences of ERD and ERQ expression in the different kinds ofbreast tissues, to exanine the possible predominant subtype in orderto proYide experimenta1 basis for se1ective hormone replacementtherapy in reducing the danger of breast cancer. The researchinc1udes two part. First, reYerse transcription--po1roerase chainreaction (RT--PCR) method was utilized to examine and quantitate ERD M and ER Q InRN expression 1eye1s in human norma1 breast, benignhyperp1asia and breast cancer tissue samp1es. Secondly, ER D proteinand ER Q protein expression leve1s and their 1ocation in differenthuman breast tissue were detected by streptayidin peroxidaseconjugated (SP) inununohistochemistry assay.Part 1. Expression of estrogen receptor Q and D InRNin human breast tissueMateria1s and Methods The tissue saInPles from 17 women primarybreast cancer, 17 benign breast disease (inc1uding 6 breasthyperplasia and l1 breast fibroadenoma) and 16 normal breast tissuesmples were obtained during surgery and stored under --80'C. Areverse transcription--po1ymerase chain reaction (RT--PCR) method wasutilized to exaJnine and quantitate ER P mRNA and ER Q mRNA expression1eye1s in those breast tissue.Resu1ts Human normal breast, benign disease and breast cancertissues expressed ER Q mRNA and/or ER D mRNA in different pos itiye rate.The positiye rate of ERD mRNA is significant1y higher than that ofER a InRN in normal breast. The ER Q InRNA positiye rate of norma1 breastis significantly lower than that of benign breast disease and breastcancer (P<0. 01), and the positiye rate of ERP mRNA in breast cancersignificantly decreased (P<0. 05). Semi--quantitative PCR showed thatthe expression leve1 of ER Q mRNA in breast cancer (l. 77i0. 49) wassignificantly higher than those in benign disease and norma1breast (1. 07l0. 35 VS 1. 06f0. 18 respective1y, P<0. 05), whi1e theexpression leye1 of ER D mRNA in breast cancer (0. 4l f 0. l6) wassignificant1y 1ower than those in benign disease and norma1breast (1. 04l0. 37 VS 1. 4l l0. 57 respectiye1y, P<0. 05). There was nosignificant difference between benign disease and normal breast inER D W $ER a mRNA expression 1eve1s.Part 2. Expression of estrogen receptor Q and...