Anti-Mouse anti-Tap63 [TAp63-5.1] monoclonal antibody
Invented at Moravian Biotechnology
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Info
| Catalogue Number | 160737 |
| Applications | N/A |
| Antigen/Gene or Protein Targets | TAp63 |
| Synonyms | transactivation domain of tumor protein p63 |
| Reactivity | Mouse |
| Host | Mouse |
| Immunogen | TAp63α |
| Positive Control | IgG2b |
| Notes |
Mammary stem cells (MaSCs) have key roles in the development of breast cancer, in its progression and in the effectiveness of breast cancer therapy. Upstream genes controlling this process are still poorly understood. One critical transcription factor involved in epithelial stem cell maintenance of the mammary gland and skin is the p53 family member and tumor-suppressor gene, p63. p63 is composed of multiple isoforms with overlapping and unique activities. It is important to note that p63 is used as a diagnostic marker in metaplastic breast cancer with no regard to the existence or activities of p63 isoforms, and research to date has been focused on the highly expressed isoform, ΔNp63. The p63 isoforms can be placed into two groups: the transactivation domain isoforms, which structurally resemble p53 and act as tumor suppressors, and the ΔN isoforms, which bind to p53, TAp63 and TAp73 and inhibit their function, thus acting as oncogenes. In the skin, TAp63 is required to maintain adult dermal stem cells and epidermal progenitor cells, required for wound healing and hair regeneration, in quiescence. ΔNp63 also has an important role in the skin. Its expression in the basal compartment of the epidermis is required for epidermal stratification and terminal differentiation in the developing and adult skin. Likewise, the expression patterns of the TAp63 and ΔNp63 isoforms of p63 in distinct mammary progenitor and stem cells suggest different roles for these isoforms in mammary gland development and homeostasis. Although ΔNp63 is highly expressed in basal cells and is critical for mammary gland development and maturation, the roles of TAp63 have not been investigated in vivo using knockout mouse models. Additionally, mechanisms for TAp63 regulation in MaSCs and how this may impinge on mammary tumorigenesis have yet to be elucidated and are critical for further understanding of how p63 can be used as a diagnostic marker for breast cancer and for therapy. Recent studies have shed light on functions for the p63 isoforms in breast cancer. TAp63 is not expressed or is present at low levels in high-grade mammary adenocarcinoma, and regulation of microRNA biogenesis through transcriptional regulation of Dicer has been implicated in its ability to suppress tumor progression and metastasis. Other mechanisms for p63’s role as a suppressor of tumorigenesis and metastasis have also been shown, including integrin recycling and interactions with transforming growth factor-β. In mouse models, TAp63-deficient mice are highly prone to metastatic mammary adenocarcinoma. Mechanisms regulating MaSCs and breast cancer stem cells (CSCs) or TICs have not been completely delineated. For example, aggressive luminal breast cancer subtypes can acquire basal cell and CSC features during their progression, and basal cell breast cancer may originate from luminal cells. Recent studies have also revealed that normal breast stem cells and CSCs share some regulatory mechanisms in certain types of breast cancer. For example, coexpression of Sox9 and Slug is sufficient to convert luminal mammary cells into MaSCs capable of mammary gland reconstitution and tumor development. Additionally, coexpression of Sox9 and Slug were found to be predictive CSC markers and promoted tumor development and metastasis. TAZ, a transducer of the Hippo pathway, has been shown to also confer CSC properties onto mammary epithelial cells (MECs) through regulation of genes that regulate cell polarity, such as Scribble (Scrib). Although it is clear that developmental genes such as p63 regulate MaSCs and the development of breast cancer, the complexity of genes such as p63 with its many isoforms and duplicitous activities in tumorigenesis make it essential to further dissect their functions in the regulation of MaSCs in cancer. Similar to the p63 isoforms, components of the Hippo pathway have been implicated in breast cancer and progression. The Hippo pathway functions to regulate cell proliferation, stem cell properties, cell polarity and tumorigenesis. Some cross-talk between p63 and the Hippo pathway has been discovered recently. ΔNp63 directly interacts with the Hippo effector YAP and is a mediator of YAP function in the epithelium of lung airways. Additionally, LKB1, a transcriptional target of TAp63 in the liver, is mutated in breast cancers and serves to maintain cell polarity through upstream regulation of Scrib and TAZ, a transducer of the Hippo pathway. Moreover, TAZ has been shown to confer CSC properties of MECs through regulation of Scrib and cell polarity. Although connections between cell polarity, the Hippo pathway and the properties of MaSCs have been well established, the upstream regulation of this process by TAp63 was previously not known. PMID: 27869165 |
| Research Area | Cancer |
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