The HOXB7 protein renders breast cancer cells resistant to tamoxifen through activation of the EGFR pathway

Jin, Kideok; Kong, Xiangjun; Shah, Tariq; Penet, Marie‐France; Wildes, Flonné; Sgroi, Dennis; Ma, Xiao‐Jun; Huang, Yi; Kallioniemi, Anne; Landberg, Göran; Bièche, Ivan; Wu, Xinyan; Lobie, Peter E.; Davidson, Nancy E.; Bhujwalla, Zaver M.; Zhu, Tao; Sukumar, Saraswati

doi:10.1073/pnas.1018859108

Cited by 109 publications

(109 citation statements)

References 32 publications

Supporting

Mentioning

105

Contrasting

Order By: Relevance

“…The expression of HOX genes keeps to temporal and spatial colinearity in embryonic development (Shah and Sukumar, 2010). Aberrant expression of HOX genes was found in various types of cancer, such as ovarian cancer (Yamashita et al, 2006), leukemia (Chang et al, 1997), breast cancer (Jin et al, 2012), cervical cancer (How et al, 2013), prostate cancer (Rubin et al, 2007), melanoma (Care et al, 1996), oral squamous cell cancer (De Souza Setubal Destro et al, 2010) and esophageal squamous cell cancer (Gu et al, 2009). However, the detailed relationship between HOX genes and tumorigenesis remains unclear (Shah and Sukumar, 2010).…”

Section: Hoxb7 Predicts Poor Clinical Outcome In Patients With Advancmentioning

confidence: 99%

HOXB7 Predicts Poor Clinical Outcome in Patients with Advanced Esophageal Squamous Cell Cancer

Long

Zhou²,

Zhang³

et al. 2014

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

Background: Esophageal squamous cell carcinoma (ESCC) accounts for most esophageal cancer in Asia, and is the sixth common cause of cancer-related deaths worldwide. Previous studies indicated HOXB7 is overexpressed in ESCC tissues, but data on prognostic value are limited. Methods: A total of 76 advanced ESCC cases were investigated. Immunohistochemistry (IHC) was used to detect the expression levels of HOXB7 and Kaplan-Meier curves and Cox regression models to determine prognostic significance. Stratified analysis was also performed according to lymph node (LN) status. Results: Kaplan-Meier curve analysis indicated that HOXB7 positive patients had significantly shorter overall survival (OS) than HOXB7 negative patients. Multivariate analysis using the Cox proportional hazards model indicated only TNM stage and HOXB7 expression to be independent predictors of overall survival of advanced ESCC patients. HOXB7 indicated poor OS in both lymph node negative (LN−) and lymph node positive (LN+) patients. Conclusion: HOXB7 predicts poor prognosis of advanced ESCC patients and can be applied as an independent prognostic predictor.

show abstract

Section: Hoxb7 Predicts Poor Clinical Outcome In Patients With Advancmentioning

confidence: 99%

HOXB7 Predicts Poor Clinical Outcome in Patients with Advanced Esophageal Squamous Cell Cancer

Long

Zhou²,

Zhang³

et al. 2014

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

show abstract

“…In addition, HOXA5 and HOXA9 have been implicated as regulators of p53 and breast cancer 1 (BRCA1), respectively, which are important factors in cancer development (54,55). Furthermore, the function of HOXA1, -B7 and -B9 in breast tumorigenesis has been investigated; HOXB7 was identified as a key factor regulating cell proliferation, invasion and tamoxifen resistance (56)(57)(58), and the overexpression of HOXA1 and HOXB9 contributed to breast cancer tumorigenicity (59,60). Additional studies have reported an association between poor prognosis and overexpression of HOXD3 and HOXB13 (61,62).…”

Section: Hox Genes and Cancermentioning

confidence: 99%

“…HOXB7 is able to promote cell proliferation in different types of tumors through its high levels of expression (83)(84)(85). In addition, HOXB7 has been demonstrated to be an oncogene (57,83,86,87), and its involvement is essential in various forms of cancer.…”

Section: Hotairmentioning

confidence: 99%

The function of homeobox genes and lncRNAs in cancer

Wang¹,

Dang²,

Liu³

et al. 2016

Oncology Letters

View full text Add to dashboard Cite

Abstract. Recently, the homeobox (HOX) gene family has been reported as a factor in tumorigenesis. In the human genome, the HOX gene family contains 4 clusters with 39 genes and multiple transcripts. Mutation or abnormal expression of genes is responsible for developmental disorders. In addition, changes in the levels and activation of certain HOX genes has been associated with the development of cancer. Long non-coding RNAs (lncRNAs) have also been identified to serve critical functions in cancer. Although a limited number of lncRNAs have been previously investigated, the list of functional lncRNA genes has recently grown. Two of the most important and well-studied lncRNAs and HOX transcript genes are HOX transcript antisense RNA (HOTAIR) and HOXA distal transcript antisense RNA (HOTTIP). The present study aimed to review not only the function of the HOTAIR and HOTTIP genes in certain forms of cancer, but also to review other HOX genes and protein functions in cancer, particularly HOX family genes associated with lncRNAs.

show abstract

“…In ER + breast cancer cell lines, HOXB7 overexpression confers tamoxifen resistance by cross talk with the EGFR signaling pathway, suggesting that HOXB7 could be a regulator of the estrogen independent breast cancer cell phenotype. Targeting this gene may improve response to tamoxifen [25].…”

mentioning

confidence: 99%

BP1, a Potential Biomarker for Breast Cancer Prognosis

et al. 2018

View full text Add to dashboard Cite

Homeobox genes are critical in tumor development. An isoform protein of DLX4 called BP1 is expressed in 80% of invasive ductal breast carcinomas. BP1 overexpression is implicated in an aggressive phenotype and poor prognosis. BP1 upregulation is associated with estrogen receptor negativity so those tumors do not respond to antiestrogens. Breast cancer is the second leading cause of death in women. BP1 could serve as both a novel prognostic biomarker for breast cancer and a therapeutic target. In this review, we address the role of BP1 protein in tumorigenesis of breast cancer and four other malignancies. A number of functions of BP1 in cancer are also discussed. Female breast cancer represents 14.6% of all new cancer cases in the USA according to the National Cancer Institute [1]. An estimated 252,710 new cases of invasive breast cancer are expected to be diagnosed in women in the USA in 2017. It is also estimated that 30% of newly diagnosed cancers in women will be breast cancers [2].Breast cancer is a hormone-dependent cancer, and estrogen (17β-estradiol) plays a critical role in the initiation and the progression of this disease [3]. Estrogen, produced by the ovaries, affects the growth and function of mammary glands by binding to the estrogen receptors (ERs) α and β. Through dimerization of the receptor, translocation to the nucleus and interaction with estrogen response elements in the promoter region of targeted genes, gene expression leads to multiple biological outcomes [4]. 70% of invasive breast cancers are ER positive (ER + ), making antiestrogens essential in treating these patients [5]. Targeting the ER or its pathway using tamoxifen (a selective ER modulator) or fulvestrant (an ER downregulator) have been successful therapeutic strategies [6]. However, drug resistance remains a major challenge in treating breast cancer. The main pathway leading to resistance involves loss of ER expression or selection of an ER-negative population of cells. Moreover, these ER-negative breast cancers have a higher histologic grade and a higher proliferative rate and are associated with poorer prognosis. This highlights the key importance of finding alternative targets to treat these patients and identifying a new biomarker for breast cancer prognosis.BP1 protein, an isoform of DLX4, belongs to the homeobox gene family which includes regulatory genes implicated in early development and cell differentiation that are frequently dysregulated in cancer [7]. Therefore, targeting BP1 may provide a new avenue for breast cancer management. The first related paper was published in 1998, when the authors mapped this new homeobox gene to chromosome 17q21 and characterized its role in repression of the β-globin gene [8]. During the last 20 years, several studies have been carried out to measure BP1 levels in breast cancer and other carcinomas, with the primary aim of confirming its diagnostic and prognostic value as a biomarker. We are writing this review to consolidate and update all of the available information on BP1. Homeobox...

show abstract

The HOXB7 protein renders breast cancer cells resistant to tamoxifen through activation of the EGFR pathway

Cited by 109 publications

References 32 publications

HOXB7 Predicts Poor Clinical Outcome in Patients with Advanced Esophageal Squamous Cell Cancer

HOXB7 Predicts Poor Clinical Outcome in Patients with Advanced Esophageal Squamous Cell Cancer

The function of homeobox genes and lncRNAs in cancer

BP1, a Potential Biomarker for Breast Cancer Prognosis

Contact Info

Product

Resources

About