In vitro study of anti-ER positive breast cancer effect and mechanism of 1,2,3,4-6-pentyl-O-galloyl-beta-d-glucose (PGG)

HOXA5 is a homeobox-containing gene associated with the development of the lung, gastrointestinal tract, and vertebrae. Here, we investigate potential roles and the gene regulatory mechanism in HOXA5 in breast cancer cells. Our studies demonstrate that HOXA5 expression is elevated in breast cancer tissues and in estrogen receptor (ER)-positive breast cancer cells. HOXA5 expression is critical for breast cancer cell viability. Biochemical studies show that estradiol (E2) regulates HOXA5 gene expression in cultured breast cancer cells in vitro. HOXA5 expression is also upregulated in vivo in the mammary tissues of ovariectomized female rats. E2-induced HOXA5 expression is coordinated by ERs. Knockdown of either ERα or ERβ downregulated E2-induced HOXA5 expression. Additionally, ER co-regulators, including CBP/p300 (histone acetylases) and MLL-histone methylases (MLL2, MLL3), histone acetylation-, and H3K4 trimethylation levels are enriched at the HOXA5 promoter in present E2. In summary, our studies demonstrate that HOXA5 is overexpressed in breast cancer and is transcriptionally regulated via estradiol in breast cancer cells.

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Concomitant Association of T-DM1 and Radiation: An In Vitro Study on HER2 Positive Cells of Breast Cancer

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2018.07.679 ◽

2018 ◽

Vol 102 (3) ◽

pp. e186

Author(s):

F. Mignot ◽

P. Verrelle ◽

Y. Kirova ◽

F. Megnin-Chanet

Keyword(s):

Breast Cancer ◽

In Vitro Study ◽

Vitro Study ◽

Her2 Positive

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SET Overexpression is Associated with Worse Recurrence-Free Survival in Patients with Primary Breast Cancer Receiving Adjuvant Tamoxifen Treatment

Journal of Clinical Medicine ◽

10.3390/jcm7090245 ◽

2018 ◽

Vol 7 (9) ◽

pp. 245 ◽

Cited By ~ 5

Author(s):

Yu-Hsiang Huang ◽

Pei-Yi Chu ◽

Ji-Lin Chen ◽

Chun-Teng Huang ◽

Chia-Han Lee ◽

...

Keyword(s):

Breast Cancer ◽

Protein Phosphatase ◽

Tamoxifen Treatment ◽

Adjuvant Tamoxifen ◽

Recurrence Free Survival ◽

Free Survival ◽

Er Positive ◽

Phosphatase 2A ◽

Positive Breast Cancer

Adjuvant tamoxifen reduces the recurrence rate of estrogen receptor (ER)-positive breast cancer. Previous in vitro studies have suggested that tamoxifen can affect the cancerous inhibitor of protein phosphatase 2A (CIP2A)/protein phosphatase 2A (PP2A)/phosphorylation Akt (pAkt) signaling in ER-negative breast cancer cells. In addition to CIP2A, SET nuclear proto-oncogene (SET) oncoprotein is another intrinsic inhibitor of PP2A, participating in cancer progression. In the current study, we explored the clinical significance of SET, CIP2A, PP2A, and Akt in patients with ER-positive breast cancer receiving adjuvant tamoxifen. A total of 218 primary breast cancer patients receiving adjuvant tamoxifen with a median follow-up of 106 months were analyzed, of which 17 (7.8%) experienced recurrence or metastasis. In an immunohistochemical (IHC) stain, SET overexpression was independently associated with worse recurrence-free survival (RFS) (hazard ratio = 3.72, 95% confidence interval 1.26–10.94, p = 0.017). In silico analysis revealed mRNA expressions of SET, PPP2CA, and AKT1 significantly correlated with worse RFS. In vitro, SET overexpression reduced tamoxifen-induced antitumor effects and drove luciferase activity in an Estrogen receptor element (ERE)-dependent manner. In conclusion, SET is a prognostic biomarker in patients with primary ER-positive breast cancer receiving adjuvant tamoxifen and may contribute to the failure of the tamoxifen treatment by modulating the ER signaling. Our study warrants further investigation into the potential role of SET in ER-positive breast cancer.

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