Identification of ten exon deleted ERβ mRNAs in human ovary, breast, uterus and bone tissues: alternate splicing pattern of estrogen receptor β mRNA is distinct from that of estrogen receptor α

Poola, Indira; Abraham, Jessy; Baldwin, Kate M.

doi:10.1016/s0014-5793(02)02521-8

Cited by 83 publications

(70 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…31,32 Interestingly, in breast, 25 ovary 25-28 and endometrium, 29 malignancy is associated with loss of ERb expression while in adenocarcinoma of the esophagus 30 increased expression is seen. One study has shown decreased ERb expression in colonic adenocarcinoma 31 while another study 32 suggests that, as [33][34][35] as well as evidence that the interaction of ERa and ERb levels may play a role in carcinogenesis. 28 The demonstration of ERb in vascular neoplasms suggests a role for estrogen antagonists in the therapy of the most aggressive vascular tumors: angiosarcomas.…”

Section: Discussionmentioning

confidence: 99%

Estrogen receptor β expression in vascular neoplasia: an analysis of 53 benign and malignant cases

et al. 2004

View full text Add to dashboard Cite

The importance of estrogen in vascular neoplasia is suggested by a predilection for women and a tendency for rapid growth during pregnancy. Although early experiments using radioligand assays demonstrated estrogen receptor (ER) expression, these findings were not confirmed by subsequent immunohistochemical studies which were performed with antibodies raised against ERa. A newly discovered estrogen receptor subtype, ERb, has not been previously characterized in vascular lesions. In order to verify the expression of estrogen receptors in vascular neoplasms as well as to clarify the inconsistency between radioligand and early immunohistochemical studies, we examined a series of 53 benign and malignant vascular neoplasms for ERb expression. All of the subtypes of vascular neoplasia examined had nuclear expression of ERb. The majority of cases (94%) displayed 2 þ to 3 þ staining. The discrepancy between radioligand studies and previous immunohistochemical studies is attributable to the use of antibodies raised against ERa, which is not expressed in vascular lesions, and not ERb, which is broadly expressed in both benign and malignant vascular neoplasms. Although ERb may be of limited diagnostic use in vascular neoplasia due to its broad expression, the potential exists for a therapeutic approach using ER agonists. The role of estrogen in vascular neoplasia has long been suspected due to the observation that vascular neoplasms tend to grow rapidly during pregnancy and in adolescence. 1 These clinical observations were initially substantiated by early experiments in the 1980s using radioligand assays, which confirmed the presence of the estrogen receptor (ER) in vascular tumors; 2,3 however, with the advent of immunohistochemical techniques, subsequent studies performed in the 1990s with antibodies raised against the ER refuted these earlier data and it appeared that the newer technology had exposed the limitations of the older biochemical assays. [4][5][6][7] Recently, an additional ER subtype, estrogen receptor beta (ERb), 8 was identified and the previous ER against which the original antibodies were raised was renamed estrogen receptor alpha (ERa). Although ERa has been assessed immunohistochemically in vascular neoplasms and found to be absent, ERb has not been previously characterized in these entities. In order to verify the expression of ER in vascular tumors as well as to clarify the inconsistency between radioligand and early immunohistochemical studies, we examined a series of 53 benign and malignant vascular neoplasms for ERb expression. Materials and methodsIn all, 22 cases of angiosarcoma, three cases of Kaposi sarcoma, one case of epithelioid hemangioendothelioma, two cases of spindle-cell hemangioma, four cases of infantile hemangioendothelioma, 13 cases of hemangioma, seven cases of lymphangioma and one case of papillary endothelial hyperplasia were identified and retrieved from the paraffin archives of the University of Chicago. Formalin-fixed paraffin-embedded specimens were cut into 4-mm sections an...

show abstract

Section: Discussionmentioning

confidence: 99%

Estrogen receptor β expression in vascular neoplasia: an analysis of 53 benign and malignant cases

et al. 2004

View full text Add to dashboard Cite

show abstract

“…all of the cell lines were found to express a 52-54 kda protein (the reported size for Erβ1). certain cell lines also expressed a smaller molecular weight band that may be an Erβ spliced variant (46,(57)(58)(59).…”

Section: Er Mrna Expression Using Rt-pcrmentioning

confidence: 99%

Analysis of estrogen receptor isoforms and variants in breast cancer cell lines

Al‐Bader

Ford

Al-Ayadhy

et al. 2011

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Abstract. in the present study, the expression of estrogen receptor (Er)α and Erβ isoforms in Er-positive (mcF7, t-47d and Zr-75-1) and Er-negative (mda-mB-231, SK-Br-3, mda-mB-453 and hcc1954) breast cancer cell lines was investigated. Erα mrna was expressed in Er-positive and some Er-negative cell lines. Erα ∆3, ∆5 and ∆7 spliced variants were present in mcF7 and t-47d cells; Erα ∆5 and ∆7 spliced variants were detected in ZR-75-1 cells. mda-mB-231 and hcc1954 cells expressed Erα ∆5 and ∆7 spliced variants. the Erβ1 variant was expressed in all of the cell lines and the Erβ2 variant in all of the Er-positive and some Er-negative cell lines (mda-mB-231, mda-mB-453 and SK-Br-3). mcF7, Zr-75-1, mda-mB-453, hcc1954 and t-47d cells expressed Erβ5. all cell lines expressed an Erα 66-kda protein band, and some expressed the truncated 42-kda variant. Erβ1 was detected in all of the cell lines in addition to a 38-44 kda variant. the results indicate that breast cancer cell lines widely used in research and reported as being Er-negative express Erα and/or Erβ mrna and protein.

show abstract

“…MCF-7 cells have an epithelial morphology, are adherent, and form a monolayer in culture. These cells express both estrogen receptor (ER)α and ERβ (Brooks et al, 1973, Enmark et al, 1997, Fuqua et al, 1999, Leygue et al, 1999, Fasco et al, 2000, Poola et al, 2000, Yoshida et al, 2000, Lespagnard et al, 2001, Poola et al, 2002 and (WT) PTEN (Li et al, 1998, Lu et al, 1999, Weng et al, 1999, Clark et al, 2002. MCF-7 cells were obtained from the American Type Culture Collection (ATCC) (Manassas, VA).…”

Section: Cell Culturementioning

confidence: 99%

Alteration of Akt activity increases chemotherapeutic drug and hormonal resistance in breast cancer yet confers an achilles heel by sensitization to targeted therapy

McCubrey

Sokolosky

Lehmann

et al. 2008

Advances in Enzyme Regulation

View full text Add to dashboard Cite

The PI3K/PTEN/Akt/mTOR pathway plays critical roles in the regulation of cell growth. The effects of this pathway on drug resistance and cellular senescence of breast cancer cells has been a focus of our laboratory. Introduction of activated Akt or mutant PTEN constructs which lack lipid phosphatase [PTEN(G129E)] or lipid and protein phosphatase [PTEN(C124S)] activity increased the resistance of the cells to the chemotherapeutic drug doxorubicin, and the hormonal drug tamoxifen. Activated Akt and PTEN genes also inhibited the induction of senescence after doxorubicin treatment; a phenomenon associated with unrestrained proliferation and tumorigenesis. Interference with the lipid phosphatase domain of PTEN was sufficient to activate Akt/mTOR/p70S6K as MCF-7 cells transfected with the mutant PTEN gene lacking the lipid phosphatase activity [PTEN(G129E)] displayed elevated levels of activated Akt and p70S6K compared to empty vector transfected cells. Cells transfected with mutant PTEN or Akt constructs were hypersensitive to mTOR inhibitors when compared with the parental or empty vector transfected cells. Akt-transfected cells were cultured for over two months in tamoxifen from which tamoxifen and doxorubicin resistant cells were isolated that were >10-fold more resistant to tamoxifen and doxorubicin than the original Akt-transfected cells. These cells had a decreased induction of both activated p53 and total p21 Cip1 upon doxorubicin treatment. Furthermore, these cells had an increased inactivation of GSK-3β and decreased expression of the estrogen receptor-α. In these drug resistant cells, there was an increased activation Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errorsmaybe discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. of ERK which is associated with proliferation. These drug resistant cells were hypersensitive to mTOR inhibitors and also sensitive to MEK inhibitors, indicating that the enhanced p70S6K and ERK expression was relevant to their drug and hormonal resistance. Given that Akt is overexpressed in greater than 50% of breast cancers, our results point to potential therapeutic targets, mTOR and MEK. These studies indicate that activation of the Akt kinase or disruption of the normal activity of the PTEN phosphatase can have dramatic effects on activity of p70S6K and other downstream substrates and thereby altering the therapeutic sensitivity of breast cancer cells. The effects of doxorubicin and tamoxifen on induction of the Raf/MEK/ERK and PI3K/Akt survival pathways were examined in unmodified MCF-7 breast cells. Doxorubicin was a potent inducer of activated ERK and to a lesser extent Akt. Tamoxifen also in...

show abstract

Identification of ten exon deleted ERβ mRNAs in human ovary, breast, uterus and bone tissues: alternate splicing pattern of estrogen receptor β mRNA is distinct from that of estrogen receptor α

Cited by 83 publications

References 40 publications

Estrogen receptor β expression in vascular neoplasia: an analysis of 53 benign and malignant cases

Estrogen receptor β expression in vascular neoplasia: an analysis of 53 benign and malignant cases

Analysis of estrogen receptor isoforms and variants in breast cancer cell lines

Alteration of Akt activity increases chemotherapeutic drug and hormonal resistance in breast cancer yet confers an achilles heel by sensitization to targeted therapy

Contact Info

Product

Resources

About