Correlation of thyroid hormone, retinoid X, peroxisome proliferator-activated, vitamin D and oestrogen/progesterone receptors in breast carcinoma

Ditsch, Nina; Mayr, Doris; Lenhard, Miriam; Strauss, Carolin; Vodermaier, Andrea; Gallwas, Julia; Stoeckl, Doris; Graeser, Monika; Weißenbacher, Tobias; Friese, Klaus; Jeschke, Udo

doi:10.3892/ol.2012.799

Cited by 20 publications

(27 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In our study, VDR expression was detected in all three samples (T7, T11 and T16), and in accordance VDR expression was previously demonstrated in a high percentage of breast cancer samples (Lyra et al, 2006;Bortman et al, 2002;Ditsch et al, 2012). In the present xenografts CYP24A1 mRNA expression was increased by 10 to 18 fold upon calcitriol treatment, demonstrating induction of the genomic vitamin D pathway.…”

Section: Discussionsupporting

confidence: 91%

Orthotopic tumorgrafts in nude mice as a model to evaluate calcitriol effects in breast cancer

et al. 2017

View full text Add to dashboard Cite

Calcitriol antiproliferative effects were observed in xenografts of breast cancer cell lines, however they were not yet investigated in tumorgrafts, consisting of freshly collected breast cancer samples xenografted into animals. Objectives: To establish a tumorgraft model, from freshly collected breast cancer samples, which were directly implanted in nude mice, to study calcitriol effects. Methods: Breast cancer samples collected from 12 patients were orthotopically implanted into nude mice. Animals were treated with weekly intratumoral injections of calcitriol 3 μg/Kg, which was previously shown to induce peak serum calcitriol levels in the predicted therapeutic range. Results: Success engraftment rate was 25%. Tumorgrafts were established from aggressive (HER2 positive or histological grade 3) highly proliferative samples and original tumor characteristics were preserved. Calcitriol highly induced its target gene, CYP24A1, indicating that the genomic vitamin D pathway is active in tumorgrafts. However, no differences in the expression of proliferation and apoptosis markers (BrdU incorporation, Ki67, CDKN1A, CDKN1B, BCL2 expression) were observed in these highly proliferative tumor samples. Conclusions: Tumorgrafts seem a promising model to explore other calcitriol doses and regimens, considering the heterogeneity of the disease and microenvironment interactions.Keywords: tumorgraft, breast cancer, calcitriol, proliferation. Modelo de enxerto tumoral ortotópico em camundongos para avaliar os efeitos do calcitriol em câncer de mama ResumoOs efeitos antiproliferativos de calcitriol foram observados em xenotransplantes de linhagens celulares de câncer de mama, entretanto, não foram ainda investigados em enxertos tumorais, consistindo de implantes em animais de amostras de câncer de mama recém-coletadas. Objetivos: Estabelecer modelo de enxerto tumoral, a partir de amostra de câncer de mama recém-coletada e diretamente implantada em camundongos nude, para estudar o efeito do calcitriol. Métodos: Amostras de câncer de mama de 12 pacientes foram implantadas ortotopicamente em camundongos nude. Os animais foram tratados com injeção intratumoral semanal de calcitriol 3 μg/Kg, a qual foi previamente associada com indução de pico sérico de calcitriol dentro do intervalo de nível terapêutico. Resultados: A taxa de sucesso de pega do enxerto foi de 25%. Os enxertos tumorais foram estabelecidos de tumores agressivos com alta taxa de proliferação (HER2 positivo ou grau histológico 3) e as características do tumor original foram preservadas. O calcitriol induziu fortemente a expressão do gene alvo, CYP24A1, indicando que a via genômica da vitamina D está ativa nos enxertos tumorais, entretanto, não se observou diferenças na expressão de marcadores de proliferação e apoptose (incorporação de BrdU, expressão de Ki67, CDKN1A, CDKN1B e BCL2) nestas amostras altamente proliferativas. Conclusões: Os enxertos tumorais parecem ser um modelo promissor para explorar outros esquemas e doses de calcitriol, considerando a heteroge...

show abstract

Section: Discussionsupporting

confidence: 91%

Orthotopic tumorgrafts in nude mice as a model to evaluate calcitriol effects in breast cancer

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Although there were no statistically significant differences, a trend towards lower VDR protein expression in larger (≥3 cm) tumours was observed in canine mammary glands. In human breast cancer, the majority of studies agree that VDR expression is inversely associated to the tumour size . The fact that our result regarding the relationship between VDR expression and the tumour size has not been statistically significant may be more likely due to the low number of samples included in the study.…”

Section: Discussionmentioning

confidence: 52%

“…In human breast, VDR expression has been demonstrated in epithelial, stromal and immune cells by immunohistochemistry . Because the VDR is expressed in the mammary gland and vitamin D and its analogues have been shown to display anticarcinogenic properties, this hormone has emerged as a promising targeted therapy.…”

Section: Introductionmentioning

confidence: 99%

“…Because the VDR is expressed in the mammary gland and vitamin D and its analogues have been shown to display anticarcinogenic properties, this hormone has emerged as a promising targeted therapy. Several studies in human breast based on the relationship among VDR expression and clinicopathological characteristics, prognosis and steroid hormone receptors expression have been carried out, but they have failed to find consistent results. In dogs, studies of VDR expression in the mammary gland were not found at the time of this writing.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Vitamin D receptor expression in canine mammary gland and relationship with clinicopathological parameters and progesterone/oestrogen receptors

Sánchez-Céspedes

Fernández-Martínez

Raya

et al. 2017

Vet Comparative Oncology

View full text Add to dashboard Cite

The vitamin D receptor (VDR) belongs to the nuclear class II receptor family. VDR is a ligand transcription factor and mediates the actions of calcitriol, the active product of vitamin D synthesis. Nowadays, it is known that the biological actions of calcitriol include the capacity to modulate cancer features, such as proliferation and differentiation, apoptosis, angiogenesis, invasion and metastasis. VDR expression has been demonstrated in human breast cancer and vitamin D has emerged as a promising targeted therapy. We analyse the VDR expression in normal and neoplastic canine mammary tissue samples and its relationship with clinicopathological parameters and progesterone/oestrogens receptors (PR/ER). Expression of VDR, Ki67 (to evaluate the proliferation index, PI), PR and ER was assessed in 50 mammary gland tissue samples from 41 female dogs by immunohistochemistry. VDR-positive staining was found in the nuclei of both myoepithelial and luminal epithelial cell layers. VDR expression was higher in normal mammary tissue (37/37 cases, 100%) then followed by benign tumours (6/15 cases, 40%) and malignant tumours (9/34 cases, 26.5%) (P = .001). Female dogs aged ≥10 years had lower VDR expression compared with dogs younger (P = .017). Relationship between VDR and breed, number of tumours, tumour size, histologic subtype, histologic grade of malignancy, PI and PR and ER expression was not observed. Studies with more samples are necessary to further evaluate the possible role of VDR in the biological behaviour of canine mammary tumours, and to corroborate the possibility to use the dog as model for human breast cancer.

show abstract

“…In the last few years, histopathological evidence is accumulating on thyroid-breast relationships such as demonstration of thyroid hormone receptors immunohistochemically and TSH receptors by gel electrophoretic methods in breast cancer tissues [19][20][21]. On this background, clinicopathological correlation studies will probably improve our comprehension of the subject concretely.…”

Section: Discussionmentioning

confidence: 99%

The prevalence of benign breast diseases in patients with nodular goiter and Hashimoto’s thyroiditis

Anıl

Guney

Gürsoy

2015

J Endocrinol Invest

View full text Add to dashboard Cite

show abstract

Correlation of thyroid hormone, retinoid X, peroxisome proliferator-activated, vitamin D and oestrogen/progesterone receptors in breast carcinoma

Cited by 20 publications

References 28 publications

Orthotopic tumorgrafts in nude mice as a model to evaluate calcitriol effects in breast cancer

Orthotopic tumorgrafts in nude mice as a model to evaluate calcitriol effects in breast cancer

Vitamin D receptor expression in canine mammary gland and relationship with clinicopathological parameters and progesterone/oestrogen receptors

The prevalence of benign breast diseases in patients with nodular goiter and Hashimoto’s thyroiditis

Contact Info

Product

Resources

About