Estrogen receptor alpha (ER-α) and beta (ER-β) mRNAs in normal ovary, ovarian serous cystadenocarcinoma and ovarian cancer cell lines:: Down-regulation of ER-β in neoplastic tissues

被引:184
|
作者
Brandenberger, AW [1 ]
Tee, MK [1 ]
Jaffe, RB [1 ]
机构
[1] Univ Calif San Francisco, Ctr Reprod Endocrinol, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA
来源
关键词
D O I
10.1210/jc.83.3.1025
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The prognosis in ovarian carcinoma, the most lethal of the gynecologic neoplasms, is poor and has changed little in the last three decades. Only a small number respond to antiestrogen therapy, although the classic estrogen receptor, ER-alpha, has been identified in ovarian surface epithelium, from which approximately 90% of ovarian cancers originate. We have previously shown that ER-beta mRNA is most abundant in human fetal ovaries, suggesting that it might play an important role in ovarian development. Therefore, we investigated the mRNA levels of both ERs in normal ovaries, ovarian serous cystadenocarcinomas, granulosa cells from patients undergoing in vitro fertilization (IVF), the ovarian surface epithelium cell line IOSE-Van, and the ovarian cancer cell lines SKOV3, HEY and OCC1. Northern blots of normal and neoplastic ovaries were hybridized with an ER-beta riboprobe that spans the A/B domain. We detected two major hybridizing bands at approximately 8 and 10 kb. An RNase protection assay using the same probe revealed a single band of the expected size. Hybridizing the same blot with an ER-alpha riboprobe showed a strong hybridizing band at approximately 6.5 kb. In ovarian cancer samples, ER-beta mRNA level was decreased when compared to normal ovaries. Using 25 cycles of RT-PCR followed by Southern blotting, we found equal amounts of ER-alpha and -beta mRNAs in normal ovaries in all age groups from 33 to 75 years; however, in ovarian cancer tissue, the level of ER-alpha mRNA was similar or slightly higher, comparable to 10(3) to 10(4) copies of plasmid DNA, but ER-beta mRNA levels were markedly decreased. Granulosa cells from IVF patients expressed high levels of ER-beta mRNA. The OSE cell line expressed a low level of ER-alpha, detectable after 40 cycles of RT-PCR and no ER-beta mRNA. SKOV3 showed a low level of ER-alpha and -beta mRNAs, whereas OCC1 showed a low level of ER-beta and a relatively high level of ER-alpha. HEY did not contain detectable amounts of either ER after 40 cycles of RT-PCR. We found no evidence of differential splicing or major deletions in almost the entire coding region of ER-beta in either normal ovaries or tumor samples.
引用
收藏
页码:1025 / 1028
页数:4
相关论文
共 37 条
  • [1] Expression of ER-α and ER-β in the hamster ovary:: Differential regulation by gonadotropins and ovarian steroid hormones
    Yang, PX
    Kriatchko, A
    Roy, SK
    [J]. ENDOCRINOLOGY, 2002, 143 (06) : 2385 - 2398
  • [2] Normal and malignant human endometrium express immunohistochemically estrogen receptor alpha (ER-α), estrogen receptor beta (ER-β) and progesterone receptor (PR)
    Mylonas, I
    Jeschke, U
    Shabani, N
    Kuhn, C
    Kriegel, S
    Kupka, MS
    Friese, K
    [J]. ANTICANCER RESEARCH, 2005, 25 (3A) : 1679 - 1686
  • [3] Therapeutic modulation of estrogen receptor in ovarian cancer cells by ER-β agonist nanoparticles
    Nair, Hareesh B.
    Tamirisa, Nina
    Santhamma, Bindu
    Joseph, Agyin K.
    Rao, Perla P.
    Kirma, Nameer B.
    Liu, Ya-Guang
    Panda, Markandeswar
    Tekmal, Rajeshwar R.
    [J]. CANCER RESEARCH, 2008, 68 (09)
  • [4] Genistein Affects Estrogen Receptor Alpha (ER-α)/Estrogen Receptor Beta (ER-β) Ratio, and Nuclear Factor-Kappa Beta (NF-Κβ) in Mice Model of Endometriosis
    Sutrisno, Sutrisno
    Gayatri, Mergy
    Wiyasa, I. Wayan Arsana
    Kalsum, Umi
    Andarini, Sri
    [J]. BAHRAIN MEDICAL BULLETIN, 2021, 43 (03) : 601 - 608
  • [5] Human estrogen receptor-α (ER-α) transactivation by selective estrogen receptor modulators (SERMs) on VIT regulatory region in ER-α-negative breast cancer cell line Evsa-T transiently transfected by ER-α
    IP Nyamagana Butera
    S Hadiy
    G Leclercq
    [J]. Breast Cancer Research, 3 (Suppl 1)
  • [6] Androgen receptor (AR), estrogen receptor-alpha (ER-α) and estrogen receptor-beta (ER-β) expression in the testis of the newt, Triturus marmoratus marmoratus during the annual cycle
    Arenas, MI
    Royuela, M
    Lobo, MVT
    Alfaro, JM
    Fraile, B
    Paniagua, R
    [J]. JOURNAL OF ANATOMY, 2001, 199 : 465 - 472
  • [7] Progress in the Understanding of Estrogen Receptor Alpha Signaling in Triple-Negative Breast Cancer: Reactivation of Silenced ER-α and Signaling through ER-α36
    Al-Kabariti, Aya Y.
    Abbas, Manal A.
    [J]. MOLECULAR CANCER RESEARCH, 2023, 21 (11) : 1123 - 1138
  • [8] Expression of estrogen receptor (ER)-α and ER-β in normal and malignant prostatic epithelial cells:: Regulation by methylation and involvement in growth regulation
    Lau, KM
    LaSpina, M
    Long, J
    Ho, SM
    [J]. CANCER RESEARCH, 2000, 60 (12) : 3175 - 3182
  • [9] Estrogen receptors alpha (ER-α), beta (ER-β) and G protein-coupled receptor 30 (GPR30) in the testicular tissue of individuals with Klinefelter syndrome
    Bernardino, Raquel L.
    Alves, Marco G.
    Silva, Joaquina
    Barros, Alberto
    Ferraz, Luis
    Sousa, Mario
    Sa, Rosalia
    Oliveira, Pedro F.
    [J]. MEDICINE, 2016, 95 (10)
  • [10] Expression of Estrogen Receptors Alpha (ER-α), Beta (ER-β), and G Protein-Coupled Receptor 30 (GP-α) in Testicular Tissue of Men with Klinefelter Syndrome
    Bernardino, R. L.
    Alves, M. G.
    Silva, J.
    Barros, A.
    Ferraz, L.
    Sousa, M.
    Sa, R.
    Oliveira, P. F.
    [J]. HORMONE AND METABOLIC RESEARCH, 2016, 48 (06) : 413 - 415