Absence of Estrogen Receptor-β Expression in Metastatic Ovarian Cancer

Rutherford, Thomas J.; Brown, Wendi; Sapi, Eva; Aschkenazi, Sarit; Muñoz, Amanda; Mor, Gil

doi:10.1097/00006250-200009000-00018

Cited by 48 publications

(66 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Hillier et al (1998) have recently shown that both ERa and ERb are expressed in human normal ovarian surface epithelial cells in culture. Others and we have shown an increase in the ERa:ERb mRNA ratio in ovarian cancers compared to normal ovaries, suggesting the possible involvement of ERa-related genes in ovarian tumor progression Brandenberger et al, 1998;Rutherford et al, 2000).…”

Section: Introductionmentioning

confidence: 58%

Estrogen induction and overexpression of fibulin-1C mRNA in ovarian cancer cells

Katsaros²,

et al. 2002

View full text Add to dashboard Cite

Fibulin-1 is an extracellular matrix protein induced by estradiol in estrogen receptor (ER) positive ovarian cancer cell lines. Alternative splicing of ®bulin-1 mRNA results in four di erent variants named A, B, C and D that may have distinct biological functions. We studied the relative expression of ®bulin-1 mRNA variants and their estrogen regulation in human ovarian cancer cells. In ovarian tissues and cancer cell lines, ®bulin-1C and -1D are the predominant forms, whereas ®bulin-1A and -1B are weakly expressed. We developed a competitive PCR assay based on coampli®cation of ®bulin-1C and -1D to study the relative expression of these ®bulin-1 variants in human ovarian samples. In ovarian cancer cell lines and ovarian cancer samples, there was a marked increase in the ®bulin-1C:1D and ®bulin-1C:HPRT mRNA ratios as compared to normal ovaries. In the BG1 estrogen receptor positive ovarian cancer cell line, ®bulin-1C mRNA was induced by estradiol in a dose-and time-dependent manner. Since others and we have previously shown an increased expression of ERa as compared to ERb in ovarian cancer cells, we investigated whether ERa or ERb is involved in this induction. For this aim, MDA-MB-231 breast cancer cell line, which expresses both low basal levels of ERs and ®bulin-1, was infected with recombinant ERa or ERb encoding adenovirus and treated with estradiol. Fibulin-1C was induced by estradiol in ERa-but not ERb-infected cells, suggesting that ®bulin-1C induction is mediated through ERa. In ovarian tumors, a trend towards a correlation between ®bulin-1C and ERa expression levels was noted. In conclusion, this study showed an increased ®bulin-1C: -1D mRNA ratio in ovarian cancer cells as compared to normal ovaries. This ®nding suggests that the C variant may be involved in ovarian carcinogenesis. Fibulin-1C overexpression may thus be a clue for the understanding of a putative role of estrogens in ERa promoted ovarian tumor progression.

show abstract

Section: Introductionmentioning

confidence: 58%

Estrogen induction and overexpression of fibulin-1C mRNA in ovarian cancer cells

Katsaros²,

et al. 2002

View full text Add to dashboard Cite

show abstract

“…Neoplastic transformation is associated with changes in the type of receptor expressed and thus the response to estrogen (38). In a recently published study using the ER knockout mouse, it was shown that ER␣ is mandatory for full development of the thymus and ER␤ is required for estrogen-mediated thymic cortex atrophy and thymocyte phenotype shift seen in the female mouse (53).…”

Section: Discussionmentioning

confidence: 99%

“…6C). To determine whether the effect of the AP-1 region is ER isoform-dependent, we transfected the FasL promoter constructs into ovarian cancer Hey cells expressing only ER␤ (38) and evaluated the effect of estrogen on FasL promoter activity. Similar to what we found with the ER␣-positive cells, the absence of a functional ERE abolished the estrogenic effect.…”

Section: Differential Role Of the Ere And Ap-1 Region For Estrogen Acmentioning

confidence: 99%

Interaction of the Estrogen Receptors with the Fas Ligand Promoter in Human Monocytes

Mor

Sapi

Abrahams

et al. 2003

The Journal of Immunology

Self Cite

165

View full text Add to dashboard Cite

The predominance of autoimmune diseases among women suggests that estrogen may modulate immune function. Monocytes and macrophages are important in initiating, maintaining, and resolving inflammatory responses through cell-signaling molecules, which control immune cell survival. One important mechanism of cell survival is mediated by the Fas/Fas ligand (FasL) system. In this study, the link between estrogen, monocytes/macrophages, and the Fas/FasL system was investigated. Estrogen treatment increased FasL expression in monocytes through the binding of the estrogen receptors (ER) to the estrogen recognizing elements and AP-1 motifs present at the FasL promoter. Furthermore, estrogen induced apoptosis in monocytes expressing ERβ, but not in monocyte-differentiated macrophages expressing ERα. The expression of either ERα or ERβ and their response to estrogen in monocytes was found to be dependent on the their stage of cell differentiation. Previously, we have shown that estrogen replacement therapy in postmenopausal women decreased the number of circulating monocytes. In this study, we have characterized the molecular mechanism by which estrogen regulates monocytes homeostasis. These findings indicate that estrogen may regulate immune cell survival through the Fas/FasL system. There is biological relevance to these findings in view of studies showing that accumulation of activated monocytes is involved in the pathogenesis of conditions such as vasculititis, arteriosclerosis, and rheumatoid arthritis.

show abstract

“…Although the spectrum of mesenchymal neoplasms remains to be evaluated, ERb expression has been characterized in a number of adenocarcinomas including those of the breast, 25 ovary, [26][27][28] endometrium, 29 esophagus, 30 stomach 31 and colon. 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.…”

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

Absence of Estrogen Receptor-β Expression in Metastatic Ovarian Cancer

Cited by 48 publications

References 19 publications

Estrogen induction and overexpression of fibulin-1C mRNA in ovarian cancer cells

Estrogen induction and overexpression of fibulin-1C mRNA in ovarian cancer cells

Interaction of the Estrogen Receptors with the Fas Ligand Promoter in Human Monocytes

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

Contact Info

Product

Resources

About