TY - JOUR
T1 - Expression and Relevance of TRPS-1
T2 - A New GATA Transcription Factor in Breast Cancer
AU - Chen, Jie Qing
AU - Bao, Yi
AU - Litton, Jennifer
AU - Xiao, Li
AU - Zhang, Hua Zhong
AU - Warneke, Carla L.
AU - Wu, Yun
AU - Shen, Xiaoyun
AU - Wu, Sheng
AU - Katz, Ruth L.
AU - Sahin, Aysegul
AU - Bondy, Melissa
AU - Murray, James L.
AU - Radvanyi, Laszlo
N1 - Funding Information:
Acknowledgments This work was supported by a grant from the Cancer Vaccine Program of Sanofi Pasteur Canada to MD Anderson Cancer Center (LS2006-00015466AG). J.Q.C. is a Susan G. Komen Breast Cancer Foundation Postdoctoral Fellow. Support from NIH grants P50 CA116199 and P50 CA116199-02S1 is also appreciated. We also thank Drs. Jonathan J Li and Sara Antonia Li (Department of Pharmacology, Toxicology and Therapeutics, The University of Kansas Medical Center) for kindly providing us specimens and slides of ACI rat mammary glands.
PY - 2011/4
Y1 - 2011/4
N2 - GATA transcription factor family members have been found to play a critical role in the differentiation of many tissue types. For example, GATA-3 has been found to be highly correlated with estrogen receptor α (ER) expression and is emerging as one of the "master regulators" in breast ductal epithelial cell differentiation. Recently, we discovered another GATA family member highly prevalent in breast cancer called the trichorhinophalangeal syndrome-1 gene (TRPS-1). Using a quantitative immunohistochemistry (qIHC) approach, we found that TRPS-1 was significantly correlated with ER, PR, GATA-3, as well as HER2 expression. However, TRPS-1 was also found to be expressed in a high proportion of ER - ductal epithelial breast cancers (BCs), indicating that it may act as a ductal epithelial cell-specific transcription factor regulating cell fate at some point in the epithelial cell differentiation pathway. In keeping with this hypothesis, we found that TRPS-1 protein expression in BC above a certain threshold using qIHC correlated with markedly improved overall survival. Cox proportional hazards analysis found that both TRPS-1 and ER expression above critical threshold equally predicted for improved survival. Thus, TRPS-1 may be a powerful new positive prognostic marker in BC, and further IHC studies, as well as examination of its molecular function in ductal epithelial cell differentiation in the breast, are warranted. In this regard, data on the role of TRPS-1 in the differentiation of cells from mesenchymal precursors in other tissues, such as kidney metanephric mesenchymal cells, columnar chondrocytes, and osteoblasts, in mouse models may be useful. Indeed, these studies have found that TRPS-1 is a critical regulator of mesenchymal-to-epithelial cell transition. In the mammary gland, the restricted expression of TRPS-1 in human, mouse, and rat ductal epithelial cells suggests that it may also play a similar role during ductal luminal progenitor/stem cell differentiation. We present a model of TRPS-1 action in which it may act upstream of GATA-3 and ER on an earlier ductal epithelial progenitor cell or mammary stem cell during mammary gland development and also helps prevent reversion of ER + BC cells back into mesenchymal-like cells. This model predicts that BCs with low or no TRPS-1 expression may inherently be much less differentiated and more aggressive tumors with less favorable prognosis.
AB - GATA transcription factor family members have been found to play a critical role in the differentiation of many tissue types. For example, GATA-3 has been found to be highly correlated with estrogen receptor α (ER) expression and is emerging as one of the "master regulators" in breast ductal epithelial cell differentiation. Recently, we discovered another GATA family member highly prevalent in breast cancer called the trichorhinophalangeal syndrome-1 gene (TRPS-1). Using a quantitative immunohistochemistry (qIHC) approach, we found that TRPS-1 was significantly correlated with ER, PR, GATA-3, as well as HER2 expression. However, TRPS-1 was also found to be expressed in a high proportion of ER - ductal epithelial breast cancers (BCs), indicating that it may act as a ductal epithelial cell-specific transcription factor regulating cell fate at some point in the epithelial cell differentiation pathway. In keeping with this hypothesis, we found that TRPS-1 protein expression in BC above a certain threshold using qIHC correlated with markedly improved overall survival. Cox proportional hazards analysis found that both TRPS-1 and ER expression above critical threshold equally predicted for improved survival. Thus, TRPS-1 may be a powerful new positive prognostic marker in BC, and further IHC studies, as well as examination of its molecular function in ductal epithelial cell differentiation in the breast, are warranted. In this regard, data on the role of TRPS-1 in the differentiation of cells from mesenchymal precursors in other tissues, such as kidney metanephric mesenchymal cells, columnar chondrocytes, and osteoblasts, in mouse models may be useful. Indeed, these studies have found that TRPS-1 is a critical regulator of mesenchymal-to-epithelial cell transition. In the mammary gland, the restricted expression of TRPS-1 in human, mouse, and rat ductal epithelial cells suggests that it may also play a similar role during ductal luminal progenitor/stem cell differentiation. We present a model of TRPS-1 action in which it may act upstream of GATA-3 and ER on an earlier ductal epithelial progenitor cell or mammary stem cell during mammary gland development and also helps prevent reversion of ER + BC cells back into mesenchymal-like cells. This model predicts that BCs with low or no TRPS-1 expression may inherently be much less differentiated and more aggressive tumors with less favorable prognosis.
KW - Breast cancer
KW - GATA-3
KW - Immunohistochemistry
KW - TRPS-1
KW - Transcription factor
KW - Trichorhinophalangeal syndrome type 1
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U2 - 10.1007/s12672-011-0067-5
DO - 10.1007/s12672-011-0067-5
M3 - Article
C2 - 21761336
AN - SCOPUS:79952626758
SN - 1868-8497
VL - 2
SP - 132
EP - 143
JO - Hormones and Cancer
JF - Hormones and Cancer
IS - 2
ER -