Prognosis of Hormone-Dependent Breast Cancers: Implications of the Presence of Dysfunctional Transcriptional Networks Activated by Insulin via the Immune Transcription Factor T-bet

McCune, Kasi; Bhat‐Nakshatri, Poornima; Thorat, Mangesh A.; Nephew, Kenneth P.; Badve, Sunil; Nakshatri, Harikrishna

doi:10.1158/0008-5472.can-09-1530

Cited by 18 publications

(11 citation statements)

References 51 publications

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“…The context dependency of this interaction must be further explored to unravel the molecular mechanisms by which CTCF enhances or impedes binding of FOXA1 to DNA. The interplay between FOXA1 and ER may extend beyond the ability of FOXA1 to control ER expression and activity. Although these results suggest a positive regulatory loop between ER and FOXA1 ( Figure 2B), others have described FOXA1 to be down-regulated with oestrogen treatment [128,[156][157][158]. Providing support for FOXA1 being an ER target, a more recent analysis of the ER chromatin interaction network revealed that ER-binding sites flank the FOXA1 gene [155].…”

Section: Foxa1 Expression In Breast Cancermentioning

confidence: 94%

FOXA1: a transcription factor with parallel functions in development and cancer

2011

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When aberrant, factors critical for organ morphogenesis are also commonly involved in disease progression. FOXA1 (forkhead box A1), also known as HNF3α (hepatocyte nuclear factor 3α), is required for postnatal survival due to its essential role in controlling pancreatic and renal function. In addition to regulating a variety of tissues during embryogenesis and early life, rescue experiments have revealed a specific role for FOXA1 in the postnatal development of the mammary gland and prostate. Activity of the nuclear hormone receptors ERα (oestrogen receptor α) and AR (androgen receptor) is also required for proper development of the mammary gland and prostate respectively. FOXA1 modulates ER and AR function in breast and prostate cancer cells, supporting the postulate that FOXA1 is involved in ER and AR signalling under normal conditions, and that some carcinogenic processes in these tissues stem from hormonally regulated developmental pathways gone awry. In addition to broadly reviewing the function of FOXA1 in various aspects of development and cancer, this review focuses on the interplay of FOXA1/ER and FOXA1/AR, in normal and cancerous mammary and prostate epithelial cells. Given the hormone dependency of both breast and prostate cancer, a thorough understanding of FOXA1's role in both cancer types is critical for battling hormone receptor-positive disease and acquired anti-hormone resistance.

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Section: Foxa1 Expression In Breast Cancermentioning

confidence: 94%

FOXA1: a transcription factor with parallel functions in development and cancer

2011

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“…The ER-positive MCF-7 breast cancer cell was noted to have increased T-bet activity associated with insulin exposure, which also was associated with tamoxifen-resistance [170]. Feng and colleagues furthered this understanding by noting that ER signaling was positively associated with WHSC1, a histone methyltransferase recruited to the ERα gene by BET proteins.…”

Section: Treatment Options In Ar+ Breast Cancermentioning

confidence: 99%

AR Signaling in Breast Cancer

Rahim

O’Regan

2017

Cancers

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Androgen receptor (AR, a member of the steroid hormone receptor family) status has become increasingly important as both a prognostic marker and potential therapeutic target in breast cancer. AR is expressed in up to 90% of estrogen receptor (ER) positive breast cancer, and to a lesser degree, human epidermal growth factor 2 (HER2) amplified tumors. In the former, AR signaling has been correlated with a better prognosis given its inhibitory activity in estrogen dependent disease, though conversely has also been shown to increase resistance to anti-estrogen therapies such as tamoxifen. AR blockade can mitigate this resistance, and thus serves as a potential target in ER-positive breast cancer. In HER2 amplified breast cancer, studies are somewhat conflicting, though most show either no effect or are associated with poorer survival. Much of the available data on AR signaling is in triple-negative breast cancer (TNBC), which is an aggressive disease with inferior outcomes comparative to other breast cancer subtypes. At present, there are no approved targeted therapies in TNBC, making study of the AR signaling pathway compelling. Gene expression profiling studies have also identified a luminal androgen receptor (LAR) subtype that is dependent on AR signaling in TNBC. Regardless, there seems to be an association between AR expression and improved outcomes in TNBC. Despite lower pathologic complete response (pCR) rates with neoadjuvant therapy, patients with AR-expressing TNBC have been shown to have a better prognosis than those that are AR-negative. Clinical studies targeting AR have shown somewhat promising results. In this paper we review the literature on the biology of AR in breast cancer and its prognostic and predictive roles. We also present our thoughts on therapeutic strategies.

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“…These transcription factors constitute a cell lineage-specific network that affects estrogen responsiveness as well as sensitivity to hormonal therapy. Despite the role of the ERdriven signaling cascade in the development of antiestrogen resistance, it is increasingly recognized that disruption of the ER/GATA-3/FOXA1 network represents an alternative way for breast cancer cells to acquire resistance to currently applied hormonal treatments (27). In addition, activation of other networks affects other cell types within the tumor microenvironment and contributes to tumor progression and metastasis (e.g., β-catenin/cAMP responsive element binding [CREB]-binding protein [CBP], chemokine receptors, retinoic acid receptors and many others) (28)(29)(30)(31)(32).…”

Section: O V E M B E R -D E C E M B E R 2 0 1 1 T R a N S C R I P T Imentioning

confidence: 99%

Transcription Factor Networks as Targets for Therapeutic Intervention of Cancer: The Breast Cancer Paradigm

Karamouzis

Papavassiliou

2011

Mol Med

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Prognosis of Hormone-Dependent Breast Cancers: Implications of the Presence of Dysfunctional Transcriptional Networks Activated by Insulin via the Immune Transcription Factor T-bet

Abstract: Estrogen receptor α (ERα)-positive breast cancers that co-express transcription factors GATA-3 and FOXA1 have a favorable prognosis. These transcription factors form an autoregulatory hormonal network that influences estrogen responsiveness and sensitivity to hormonal therapy.

Cited by 18 publications

References 51 publications

FOXA1: a transcription factor with parallel functions in development and cancer

FOXA1: a transcription factor with parallel functions in development and cancer

AR Signaling in Breast Cancer

Transcription Factor Networks as Targets for Therapeutic Intervention of Cancer: The Breast Cancer Paradigm

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