Human estrogen receptor messenger RNA variants in both normal and tumor breast tissues

Gotteland, Marianne; Desauty, G.; Delarue, J; Liu, Li; May, Evelyne

doi:10.1016/0303-7207(95)03576-s

Cited by 65 publications

(38 citation statements)

References 22 publications

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“…In their aggregate, these variants are quite prominent; however, no single variant (with the possible exception of ERAE7) is ever likely to accumulate to sufficiently high levels to be easily detected at the protein level. A similar picture is likely to hold true in most human breast tumors, as evidenced by numerous published studies on ER-a variants (reviewed in 4,5,8). Unusual situations can also occur, however, as shown by our characterization of a discordant breast tumor that apparently lacks any wt ER-a and appears to exclusively express a pair of prominent ER-a mRNAs that lack exons II through V.…”

Section: Discussionsupporting

confidence: 67%

“…Recent work from this and other laboratories have shown that human breast tumors and tumor-derived cell lines contain a mixed population of estrogen receptor-a (ER-a) messenger RNAs (mRNAs), representing both correctly and aberrantly processed transcripts (1)(2)(3)(4)(5). The aberrant ER-a mRNAs are predicted to give rise to structurally altered receptor molecules that are likely to interfere with the normal estrogen response pathway present in breast tumor cells.…”

Section: Scope Of the Projectmentioning

confidence: 99%

“…As reviewed by ourselves and others (4,5,9,10), RNAs expressed from the ER-a gene in mammary epithelial tissue typically represent a mixed population of wild type and variant mRNAs, with the variants often representing 50% or more of the total ER-a transcript pool (see below). A wide variety of variant ER-a mRNAs have been described in the literature, but those most commonly observed harbor a precise deletion of one of the internal exons that contribute to the structure of the mature ER-a protein.…”

Section: Generation and Functional Analysis Of Cell Lines That Stablymentioning

confidence: 99%

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Splicing Variants of the Estrogen Receptor in Breast Cancer

Miksicek¹

1997

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Section: Discussionsupporting

confidence: 67%

Section: Scope Of the Projectmentioning

confidence: 99%

Section: Generation and Functional Analysis Of Cell Lines That Stablymentioning

confidence: 99%

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Splicing Variants of the Estrogen Receptor in Breast Cancer

Miksicek¹

1997

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“…ERh is found in both ductal, lobular epithelial and stromal cells of the rodent mammary gland (9). ERa, on the other hand, is only found in the ductal and lobular epithelial cells but not in stroma (10). It is generally believed that breast tumors, at least initially, are dependent on the stimulatory effects of estrogens.…”

Section: Introductionmentioning

confidence: 99%

“…Tamoxifen and similar antiestrogens are currently the first-line therapy for treatment of hormone-dependent breast cancer (11). Various ER transcripts have been found in breast carcinomas (10), and data exist supporting protein expression for several of these isoforms (12). Normal and cancer tissues display a variety of profiles regarding ERa, ERh, and ER splice variants at both mRNA and protein levels (13,14).…”

Section: Introductionmentioning

confidence: 99%

Estrogen Receptor β2 Negatively Regulates the Transactivation of Estrogen Receptor α in Human Breast Cancer Cells

et al. 2007

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Estrogens, by binding to and activating two estrogen receptors (ERA and ERB), are critically involved in the development of the mammary gland and breast cancer. An isoform of ERB, ERB2 (also called ERBcx), with an altered COOH-terminal region, is coexpressed with ERA in many human breast cancers. In this study, we generated a stable cell line from MCF7 breast cancer cells expressing an inducible version of ERB2, along with endogenous ERA, and examined the effects of ERB2 on the ERA protein levels and function. We showed that ERB2 inhibited ERA-mediated transactivation via estrogen response element and activator protein-1 sites of reporter constructs as well as the endogenous genes pS2 and MMP-1. Chromatin immunoprecipitation assays revealed that ERB2 expression caused a significant reduction in the recruitment of ERA to both the pS2 and MMP-1 promoters. Furthermore, ERB2 expression induced proteasome-dependent degradation of ERA. The inhibitory effects of ERB2 on ERA activity were further confirmed in HEK293 cells that lack functional endogenous ERs. We also showed that ERB2 can interact with ERA both in vitro and in mammalian cells, which is compatible with a model where ERB2/ERA heterodimers are targeted to the proteasome. Finally, in human breast cancer samples, we observed that expression of ERB2 significantly correlated with ERA-negative phenotype. Our data suggest that ERB2 could influence ERA-mediated effects relevant for breast cancer development, including hormone responsiveness. [Cancer Res 2007;67(8):3955-62]

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Expression of oestrogen receptor alpha variants in non-malignant breast and early invasive breast carcinomas

et al. 2000

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Oestrogen receptor (ER) alpha variants have been described in normal breast and breast carcinomas, but their presence in a range of benign conditions and in small early invasive breast carcinomas has not been considered. Cryostat tissue sections from 19 normal and proliferative breast lesions and 44 carcinomas 15 mm and less in size detected by mammographic screening were screened for ERalpha splice variants using reverse transcriptase-nested PCR. The carcinomas were assessed for mutation by single-stranded conformational polymorphism analysis and variant forms/band shifts were sequenced. ERalpha was detected in all 19 non-malignant cases and exon 7-deleted variants were found in 16 of them. Three cases showed weak expression of exon 5, and two of exon 3 variants. There was no relationship between the presence of variants and the extent of proliferative change, ER status or age. ERalpha mRNA was not detected in two carcinomas; exon 3 deletions were found in four (9. 5%) of the other carcinomas, exon 5 in two (4.8%), and exon 7 in 11 (26.2%), with two variants in four carcinomas and a total of 29.5% of all cases having detectable variants. Two point mutations were found in one, which was a tubular carcinoma. Variant forms were identified in carcinomas of all sizes (bar<10 mm) but were more frequent in those of 15 mm. There was no relationship with type, grade or receptor status. The main difference between non-malignant breast and early invasive cancers related to exons 3 and 5. The findings suggest that ERalpha variants are not involved in breast cancer development but occur with tumour progression and may be a consequence rather than a cause.

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Human estrogen receptor messenger RNA variants in both normal and tumor breast tissues

Cited by 65 publications

References 22 publications

Splicing Variants of the Estrogen Receptor in Breast Cancer

Splicing Variants of the Estrogen Receptor in Breast Cancer

Estrogen Receptor β2 Negatively Regulates the Transactivation of Estrogen Receptor α in Human Breast Cancer Cells

Expression of oestrogen receptor alpha variants in non-malignant breast and early invasive breast carcinomas

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