scholarly journals RASSF1A-Mediated Suppression of Estrogen Receptor Alpha (ERα)-Driven Breast Cancer Cell Growth Depends on the Hippo-Kinases LATS1 and 2

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2868
Author(s):  
Sven Roßwag ◽  
Jonathan P. Sleeman ◽  
Sonja Thaler
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Tumor Suppressor ◽  
Estrogen Receptor Alpha ◽  
Molecular Mechanisms ◽  
Hippo Pathway ◽  
Hippo Signaling ◽  
Breast Cancers ◽  
Receptor Alpha ◽  
And Function

Around 70% of breast cancers express the estrogen receptor alpha (ERα). This receptor is of central importance for breast cancer development and estrogen-dependent tumor growth. However, the molecular mechanisms that are responsible for the control of ERα expression and function in the context of breast carcinogenesis are complex and not fully understood. In previous work, we have demonstrated that the tumor suppressor RASSF1A suppresses estrogen-dependent growth of breast cancer cells through a complex network that keeps ERα expression and function under control. We observed that RASSF1A mediates the suppression of ERα expression through modulation of the Hippo effector Yes-associated protein 1 (YAP1) activity. Here we report that RASSF1A-mediated alteration of YAP1 depends on the Hippo-kinases LATS1 and LATS2. Based on these results, we conclude that inactivation of RASSF1A causes changes in the function of the Hippo signaling pathway and altered activation of YAP1, and as a consequence, increased expression and function of ERα. Thus, the inactivation of RASSF1A might constitute a fundamental event that supports the initiation of ERα-dependent breast cancer. Furthermore, our results support the notion that the Hippo pathway is important for the suppression of luminal breast cancers, and that the tumor-suppressor function of RASSF1A depends on LATS1 and LATS2.

scholarly journals Endocrine Resistance in Breast Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-27 ◽  
Author(s):  
J. M. Dixon
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Disease Resistance ◽  
Estrogen Receptor Alpha ◽  
Endocrine Resistance ◽  
Breast Cancers ◽  
Resistance To Therapy ◽  
Receptor Alpha ◽  
Number Of Patients

Around 70% of all breast cancers are estrogen receptor alpha positive and hence their development is highly dependent on estradiol. While the invention of endocrine therapies has revolusioned the treatment of the disease, resistance to therapy eventually occurs in a large number of patients. This paper seeks to illustrate and discuss the complexity and heterogeneity of the mechanisms which underlie resistance and the approaches proposed to combat them. It will also focus on the use and development of methods for predicting which patients are likely to develop resistance.

The expression and function of estrogen receptor alpha and beta in human breast cancer and its clinical application.

2003 ◽  
pp. 193-202 ◽  
Author(s):  
S-I Hayashi ◽  
H Eguchi ◽  
K Tanimoto ◽  
T Yoshida ◽  
Y Omoto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Estrogen Receptor ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Estrogen Receptor Alpha ◽  
Expression Profiles ◽  
Gene Promoters ◽  
Receptor Alpha ◽  
And Function

The overexpression of estrogen receptor alpha (ERalpha) is frequently observed in the early stage of breast cancer. We previously reported that the specific promoter of the ERalpha gene is responsible for this enhanced transcription of the gene, and identified the cis-acting elements which play an important role in its transcription. Furthermore, methylation of the ERalpha gene promoters also contribute to the regulation of gene transcription. Elucidation of these mechanisms of ERalpha gene expression may provide useful information for the early detection and chemoprevention of breast cancer. On the other hand, the expression of ERbeta has been reported in breast cancer. We have also assessed the significance and function of ERbeta and its variant types in breast cancer, and suggest that ERbeta and ERbetacx specifically suppress the function of ERalpha through different mechanisms. ERbeta isoforms may be important functional modulators of the estrogen-signaling pathway in breast cancer cells, and might affect the clinical outcome of patients. Moreover, to address the role of these ERs on the estrogen-dependent growth of breast cancer cells and to develop a diagnostic tool, we have analyzed the gene expression profiles of estrogen-responsive genes using cDNA microarray. Based on these results, the expression of several candidate genes in breast cancer tissues were analyzed by real-time RT-PCR and by immunohistochemical techniques, in order to discover new predictive factors for the endocrine therapy of patients with breast cancer. These studies could provide new clues for the elucidation of the estrogen-dependent mechanisms of cancer and the clinical benefits for patients.

scholarly journals 0188 : Molecular mechanisms involved in the vascular protection induced by estrogen receptor alpha during hypertension in the mouse

2015 ◽  
Vol 7 (2) ◽  
pp. 187-188
Author(s):  
Emmanuel Guivarc’H ◽  
Anne-Laure Guihot ◽  
Julie Favre ◽  
Emilie Vessières ◽  
Jamal Wakim ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Estrogen Receptor Alpha ◽  
Molecular Mechanisms ◽  
Vascular Protection ◽  
Receptor Alpha
Sign in / Sign up

Export Citation Format

Share Document