May 30, 2020

Combined P53/PTEN deficiency activates expression of mesenchyme homeobox 1 (MEOX1) required for growth of triple-negative breast cancer

The Journal of Biological Chemistry
Mari GasparyanDuxin Sun


Triple-negative breast cancer (TNBC) is an aggressive cancer subtype for which effective therapies are unavailable. TNBC has a high frequency of tumor protein P53 (P53) and phosphatase and tensin homolog (PTEN) deficiencies, and combined P53/PTEN deficiency is associated with poor prognosis and poor response to anticancer therapies. In this study, we discovered that combined P53/PTEN deficiency in TNBC activates expression of the transcription factor mesenchyme homeobox 1 (MEOX1). We found that MEOX1 is expressed only in TNBC deficient in P53 or PTEN and that its expression is undetectable in luminal A, luminal B, and HER2+ subtypes as well as in normal breast cells with wild type P53/PTEN. Notably, siRNA knockdown of both P53 and PTEN activated MEOX1 expression in breast cancer cells, whereas individual knockdowns of either P53 or PTEN had only minimal effects on MEOX1 expression. MEOX1 knockdown abolished cell proliferation of P53/PTEN-deficient TNBC in vitro and inhibited tumor growth in vivo, but had no effect on the proliferation of luminal and HER2+ cancer cells and of normal breast cells. RNA-Seq and immunoblotting analyses showed that the MEOX1 knockdown decreases expression of tyrosine kinase 2 (TYK2), signal transduce...Continue Reading

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Mentioned in this Paper

Transcription Factor
Protein Expression
RNA, Small Interfering
Poor Response to Treatment
Breast Cancer Cell
ErbB-2 Receptor
Pten Activity
Subtype (Attribute)

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