Changes in Radiation Sensitivity and Steroid Receptor Content Induced by Hormonal Agents and Ionizing Radiation in Breast Cancer Cells in Vitro

Paulsen, Gudrun H. U.; Strickert, Trond; Marthinsen, Anne Beate Langeland; Lundgren, Steinar

doi:10.3109/02841869609100720

Cited by 59 publications

(33 citation statements)

References 19 publications

(12 reference statements)

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“…This is supported by preclinical studies showing radiotherapy to reduce ER-expression in breast cancer cell-lines and rat mammary-tumors (22)(23)(24)(25), as well as to induce ER-negative breast cancer in premenopausal mice (26). Potential explanations could be: Activation of DNA-repair pathways influencing ER-expression (23); Disturbance of ERautoregulation involving micoRNA (27,28); Microenvironmental changes inducing an ERnegative stem-cell-enriched phenotype (29); and promoter-hypermethylation reducing estrogen binding-affinity and signaling (25,28).…”

mentioning

confidence: 50%

Prognosis, stage and oestrogen receptor status of contralateral breast cancer in relation to characteristics of the first tumour, prior endocrine treatment and radiotherapy

Alkner¹,

Ehinger²,

Bendahl³

et al. 2015

European Journal of Cancer

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Prognosis, stage and oestrogen receptor status of contralateral breast cancer in relation to characteristics of the first tumour, prior endocrine treatment and radiotherapy.Alkner, Sara; Ehinger, Anna; Bendahl, Pär-Ola; Rydén, Lisa; Fernö, Mårten Link to publication Citation for published version (APA): Alkner, S., Ehinger, A., Bendahl, P-O., Rydén, L., & Fernö, M. (2015). Prognosis, stage and oestrogen receptor status of contralateral breast cancer in relation to characteristics of the first tumour, prior endocrine treatment and radiotherapy. European Journal of Cancer, 51(16), 2304 -2313 . DOI: 10.1016 /j.ejca.2015 General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal Role of the Funding Sources:None of the funding sources had any impact on study design; the collection, analysis and interpretation of data; the writing of the report; or in the decision to submit the article for publication.3 Abstract Aim: A contralateral breast cancer (CBC) is today treated as an independent primary tumor, although recent data suggest risk and prognosis of CBC to be influenced by characteristics of and treatment given for the first tumor (BC1). We hereby investigate phenotypical and prognostic features of the second tumor (BC2) in relation to prior endocrine treatment and radiotherapy.Methods: From a well-defined population-based cohort of CBC-patients, we have constructed a unique tissue-microarray including 600 pairs of primary tumors and CBCs.Breast cancer mortality was primary end-point for prognosis. Results: Both estrogen receptor (ER) status and stage was strongly correlated between BC1and BC2 within CBC-pairs. Although BC2 had the highest prognostic impact, BC1 continued to influence prognosis after diagnosis of CBC. Patients diagnosed with two high stage tumors within a short time-interval had a particularly bad prognosis. Prior endocrine therapy and radiotherapy both correlated to ER-negativity of BC2. An ER-negative BC2 was associated with an inferior prognosis compared to an ER-positive BC2 regardless of ER-status of BC1 or prior endocrine therapy. Conclusions:Our results suggest that both the residual prognostic impact of BC1, the possibility of contralateral metastasis, as well as prior treatment given, need to be considered when determining appropriate diagnostic work-up and treatment of CBC. In addition, radiation to the contralateral breast and risk of inducing CBC with an aggressive ER-negative phenotype should be considered when establishing new radiation treatm...

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mentioning

confidence: 50%

Prognosis, stage and oestrogen receptor status of contralateral breast cancer in relation to characteristics of the first tumour, prior endocrine treatment and radiotherapy

Alkner¹,

Ehinger²,

Bendahl³

et al. 2015

European Journal of Cancer

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“…For establishment of long-term tamoxifen treatment, MCF-7 cells were exposed to low doses (0.01 -1 mM) of tamoxifen (Wako, Osaka, Japan) for 4 months, as detailed previously (Paulsen et al, 1996;Madsen et al, 1997). Anti-p53, anti-JNK1, anti-p38, anti-p21, antiBcl-2 and anti-actin antibodies were purchased from Santa Cruz Biotechnology (Santa Cruz, CA, USA) and a specific inhibitor of JNK (SP600125) from Calbiochem (San Diego, CA, USA).…”

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confidence: 99%

FADD phosphorylation is critical for cell cycle regulation in breast cancer cells

et al. 2006

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Anti-oestrogen therapy is effective for control of hormone receptor-positive breast cancers, although the detailed molecular mechanisms, including signal transduction, remain unclear. We demonstrated here that long-term tamoxifen treatment causes G2/M cell cycle arrest through c-jun N-terminal kinase (JNK) activation, which is dependent on phosphorylation of Fas-associated death domain-containing protein (FADD) at 194 serine in an oestrogen (ER) receptor-positive breast cancer cell line, MCF-7. Expression of a dominant negative mutant form of MKK7, a kinase upstream of JNK, or mutant FADD (S194A) in MCF-7 cells suppressed the cytotoxicity of long-term tamoxifen treatment. Of great interest, similar signallings could be evoked by paclitaxel, even in an ERnegative cell line, MDA-MB-231. In addition, immunohistochemical analysis using human breast cancer specimens showed a close correlation between phosphorylated JNK and FADD expression, both being significantly reduced in cases with metastatic potential. We conclude that JNK-mediated phosphorylation of FADD plays an important role in the negative regulation of cell growth and metastasis, independent of the ER status of a breast cancer, so that JNK/FADD signals might be promising targets for cancer therapy.

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“…Although minor changes in the PGR status induced by radiotherapy should not be excluded, authors demonstrated that these receptors persisted in recurrent meningiomas and even significantly increased (P!0.02; Rubinstein et al 1994). In MCF7 breast cancer cell lines, Paulsen et al (1996) demonstrated that a radiation dose of 6 Gy reduced the ER content in cytosol, but brought no alterations to the PGR content. These results support hormone treatment for non-resectable meningiomas, especially at recurrence.…”

Section: Chargari Et Al: Endocrine Therapy In Meningioma Managementmentioning

confidence: 99%

Reapprasial of the role of endocrine therapy in meningioma management

Chargari

Védrine²,

Bauduceau³

et al. 2008

Endocrine Related Cancer

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Recurrent meningiomas constitute an uncommon but significant problem after standard therapy failure. Speculation that meningiomas may be subject to endocrine influence was supported by both immunohistochemical analyses and epidemiological data. Therefore, alternative strategies such as endocrine therapy have been suggested. Although evidence of consistent findings for the role of specific hormonal exposures is mounting, there are numerous discrepancies about the mitogenic effect of hormonal manipulation on meningioma cells. A better understanding of the molecular mechanisms involved in meningioma pathogenesis may not only lead to the identification of novel diagnostic and prognostic markers but may also facilitate the development of new pathogenesis-based targeted strategies. This review of literature aims to summarize the present state of the art of endocrine therapy in the management of meningiomas, in order to establish whether hormonotherapy could be included in the therapeutic strategy for unresectable and/or progressive tumours in previously irradiated meningioma patients.

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Changes in Radiation Sensitivity and Steroid Receptor Content Induced by Hormonal Agents and Ionizing Radiation in Breast Cancer Cells in Vitro

Cited by 59 publications

References 19 publications

Prognosis, stage and oestrogen receptor status of contralateral breast cancer in relation to characteristics of the first tumour, prior endocrine treatment and radiotherapy

Prognosis, stage and oestrogen receptor status of contralateral breast cancer in relation to characteristics of the first tumour, prior endocrine treatment and radiotherapy

FADD phosphorylation is critical for cell cycle regulation in breast cancer cells

Reapprasial of the role of endocrine therapy in meningioma management

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