The Role of CHK1 Varies with the Status of Oestrogen-receptor and Progesterone-receptor in the Targeted Therapy for Breast Cancer

The oestrogen receptor is a ligand-activated transcription factor that modulates specific gene expression by binding to short DNA sequences. The study of the role of oestrogen receptor on the expression of the mitogenic actionof oestrogens and oncogenesis lead biomedical research in new approaches of the treatment of oestrogen-dependent tumors by using antioestrogens. Main mechanism of action of antioestrogens is the prevention of oestrogen action by blocking the binding of oestradiol to the oestrogen receptor. Tamoxifen, the most wellknown antioestrogen, is widely used as adjuvant therapy in all stages of human breast cancer. Recently interest is focused on the potential use of "pure" antioestrogens. The use of antioestrogens in veterinary oncology is also under discussion.

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Corrigendum to “Novel role of signal transducer and activator of transcription 3 as a progesterone receptor coactivator in breast cancer” [Steroids 76 (2011) 381–392]

Steroids ◽

10.1016/j.steroids.2011.07.003 ◽

2011 ◽

Vol 76 (12) ◽

pp. 1407

Author(s):

Cecilia J. Proietti ◽

Wendy Béguelin ◽

María Celeste Díaz Flaqué ◽

Florencia Cayrol ◽

Martín A. Rivas ◽

...

Keyword(s):

Breast Cancer ◽

Progesterone Receptor ◽

Signal Transducer ◽

Transcription 3

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Progesterone Receptor B signaling Reduces Breast Cancer Cell Aggressiveness: Role of Cyclin-D1/Cdk4 Mediating Paxillin Phosphorylation

Cancers ◽

10.3390/cancers11081201 ◽

2019 ◽

Vol 11 (8) ◽

pp. 1201 ◽

Cited By ~ 2

Author(s):

Francesca Ida Montalto ◽

Francesca Giordano ◽

Chiara Chiodo ◽

Stefania Marsico ◽

Loredana Mauro ◽

...

Keyword(s):

Breast Cancer ◽

Cell Migration ◽

Progesterone Receptor ◽

Cyclin D1 ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Breast Epithelial Cell ◽

Luminal A ◽

Progesterone Receptor B

Progesterone-Receptor (PR) positivity is related with an enhanced response to breast cancer therapy, conversely cyclin D1 (CD1) is a retained marker of poor outcome. Herein, we demonstrate that hydroxyprogesterone (OHPg) through progesterone receptor B (PR-B) reduces breast cancer cell aggressiveness, by targeting the cytoplasmic CD1. Specifically, OHPg diminishes CD1 expression by a transcriptional regulation due to the recruitment of PR-B at a canonical half-PRE site of the CD1 promoter, together with HDAC1, determining a chromatin conformation less prone for gene transcription. CD1, together with its kinase partner Cdk4, regulates cell migration and metastasis, through the association with key components of focal adhesion, such as Paxillin (Pxn). Kaplan-Meier analysis shows that low Pxn expression was associated with increased distant metastasis-free survival in luminal A PR+ breast carcinomas. Interestingly, OHPg treatment reduced Pxn content in T47-D and MCF-7 cells; besides, the interaction between endogenous cytoplasmic CD1/Cdk4 with Pxn was reduced. This was consistent with the reduction of p-Ser83Pxn levels, crucially causing the delay in cell migration and a concomitant inhibition of Rac1 activity and p-PAK. Collectively, these findings support the role of PR-B in breast epithelial cell integrity and reinforce the importance in targeting PR-B as a potential strategy to restrict breast tumor cell invasion and metastasis.

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