scholarly journals Increased expression of the HDAC 9 gene is associated with antiestrogen resistance of breast cancers

2019 ◽  
Vol 13 (7) ◽  
pp. 1534-1547 ◽  
Author(s):  
Aurélien Linares ◽  
Said Assou ◽  
Marion Lapierre ◽  
Erwan Thouennon ◽  
Céline Duraffourd ◽  
...  
Keyword(s):  
Antiestrogen Resistance ◽  
Breast Cancers

scholarly journals Proline rich 11 (PRR11) overexpression amplifies PI3K signaling and promotes antiestrogen resistance in breast cancer

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Kyung-min Lee ◽  
Angel L. Guerrero-Zotano ◽  
Alberto Servetto ◽  
Dhivya R. Sudhan ◽  
Chang-Ching Lin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Cells ◽  
Endocrine Resistance ◽  
Poor Response ◽  
Regulatory Subunit ◽  
Antiestrogen Resistance ◽  
Breast Cancers ◽  
Pi3k Inhibitors ◽  
Highly Sensitive ◽  
Causal Genes

Abstract The 17q23 amplicon is associated with poor outcome in ER+ breast cancers, but the causal genes to endocrine resistance in this amplicon are unclear. Here, we interrogate transcriptome data from primary breast tumors and find that among genes in 17q23, PRR11 is a key gene associated with a poor response to therapeutic estrogen suppression. PRR11 promotes estrogen-independent proliferation and confers endocrine resistance in ER+ breast cancers. Mechanistically, the proline-rich motif-mediated interaction of PRR11 with the p85α regulatory subunit of PI3K suppresses p85 homodimerization, thus enhancing insulin-stimulated binding of p110-p85α heterodimers to IRS1 and activation of PI3K. PRR11-amplified breast cancer cells rely on PIK3CA and are highly sensitive to PI3K inhibitors, suggesting that PRR11 amplification confers PI3K dependence. Finally, genetic and pharmacological inhibition of PI3K suppresses PRR11-mediated, estrogen-independent growth. These data suggest ER+/PRR11-amplified breast cancers as a novel subgroup of tumors that may benefit from treatment with PI3K inhibitors and antiestrogens.

scholarly journals Modulating HSF1 levels impacts expression of the estrogen receptor α and antiestrogen response

2021 ◽  
Vol 4 (5) ◽  
pp. e202000811
Author(s):  
Maruhen AD Silveira ◽  
Christophe Tav ◽  
Félix-Antoine Bérube-Simard ◽  
Tania Cuppens ◽  
Mickaël Leclercq ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Endocrine Resistance ◽  
Estrogen Receptor Α ◽  
Heat Shock Factor 1 ◽  
Antiestrogen Resistance ◽  
Breast Cancers ◽  
Proof Of Concept ◽  
Transcriptional Program ◽  
Cellular Functions

Master transcription factors control the transcriptional program and are essential to maintain cellular functions. Among them, steroid nuclear receptors, such as the estrogen receptor α (ERα), are central to the etiology of hormone-dependent cancers which are accordingly treated with corresponding endocrine therapies. However, resistance invariably arises. Here, we show that high levels of the stress response master regulator, the heat shock factor 1 (HSF1), are associated with antiestrogen resistance in breast cancer cells. Indeed, overexpression of HSF1 leads to ERα degradation, decreased expression of ERα-activated genes, and antiestrogen resistance. Furthermore, we demonstrate that reducing HSF1 levels reinstates expression of the ERα and restores response to antiestrogens. Last, our results establish a proof of concept that inhibition of HSF1, in combination with antiestrogens, is a valid strategy to tackle resistant breast cancers. Taken together, we are proposing a mechanism where high HSF1 levels interfere with the ERα-dependent transcriptional program leading to endocrine resistance in breast cancer.

Increased wound-response revealed by proteomics of estrogen receptor-negative breast cancers

2008 ◽  
Vol 68 (S 01) ◽  
Author(s):  
H Neubauer ◽  
K Sotlar ◽  
D Wallwiener ◽  
MA Cahill ◽  
E Solomayer ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Wound Response ◽  
Breast Cancers ◽  
Estrogen Receptor Negative

201Tl Scintigraphy in the Evaluation of Palpable and Nonpalpable Breast Lesions: Correlation with Mammography and Ultrasonography

1997 ◽  
Vol 36 (08) ◽  
pp. 282-288 ◽  
Author(s):  
T. Atasever ◽  
A. Özdemir ◽  
I. Öznur ◽  
N. I. Karabacak ◽  
N. Gökçora ◽  
...  
Keyword(s):  
Final Diagnosis ◽  
Lower Sensitivity ◽  
Breast Lesions ◽  
Breast Cancers ◽  
Combined Use ◽  
Malignant Breast ◽  
Malignant Lesions ◽  
Benign Breast Lesions ◽  
Palpable Breast ◽  
Metastatic Sites

Summary Aim: Our goal was to determine the clinical usefulness of TI-201 to identify breast cancer in patients with suspicious breast lesions on clinical examination, and/or abnormal radiologic (mammography and/or ultrasonography) findings. Methods: TI-201 scintigraphy were performed in sixty-eight patients with 70 breast abnormalities (51 palpable, 19 nonpalpable) and compared with mammography and ultrasonography (US). Early (15 min) and late (3 h) images of the breasts were obtained following the injection of 111 MBq (3 mCi) of TI-201. Visual and semiquantitative interpretation was performed. Results: Final diagnosis confirmed 52 malignant breast lesions and 18 benign conditions. TI-201 visualized 47 of 52 (90%) overall malignant lesions. Thirty-eight of 40 (95%) palpable and 9 of 12 (75%) nonpalpable breast cancers were detected by TI-201 scintigraphy. The smallest mass lesion detected by TI-201 measured 1.5x1.0 cm. Eleven breast lesions were interpreted as indeterminate by mammography and/or sonography. TI-201 scintigraphy excluded malignancy in 7 of 8 (88%) patients with benign breast lesions interpreted as indeterminate. Five of the 18 (28%) benign breast lesions showed TI-201 uptake. None of the fibroadenoma and fibrocystic changes accumulated TI-201. TI-201 scintigraphy, mammography and ultrasonography showed 90%, 92%, 85% overall sensitivity and 72%, 56%, 61% overall specificity respectively. Twenty-one of the 28 (75%) axillary nodal metastatic sites were also detected by TI-201. In malignant and benign lesions, early and late lesion/contralateral normal side (L/N) ratios were 1.58 ± 0.38 (mean ± SD) and 1.48 ± 0.32 (p >0.05), 1.87 ± 0.65 and 1.34 ± 0.20 (p<0.05) respectively. The mean early and late L/N ratios of malignant and benign groups did not show statistical difference (p>0.05). Conclusion: Overall, TI-201 scintigraphy was the most specific of the three methods and yielded favourable results in palpable breast cancers, while it showed lower sensitivity in nonpalpable cancers and axillary metastases. Combined use of TI-201 scintigraphy with mammography and US seems to be useful in difficult cases, such as dense breasts and indeterminate breast lesions.

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