Related Experiment Video
Updated: Jul 14, 2026
09:32
Procedure and Key Optimization Strategies for an Automated Capillary Electrophoretic-based Immunoassay Method
Published on: September 10, 2017
Relationship between p53 and p27 expression following HER2 signaling
Patrizia Casalini1, Marilena V Iorio, Valeria Berno
1Molecular Biology Unit, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy.
Breast (Edinburgh, Scotland)
|July 3, 2007
Summary
The tumor suppressor protein p53 is crucial for upregulating the cell cycle inhibitor p27 following HER2 activation in breast cancer. This finding may impact Transtuzumab therapy response.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- HER2 activation is often linked to low p27 expression in breast tumors.
- HER2 activation can upregulate p53 protein levels in tumor cells.
- The precise role of p53 in the HER2-p27 relationship remains unclear.
Purpose of the Study:
- To investigate the role of p53 in mediating the connection between HER2 and p27 expression.
- To determine if p53 influences p27 levels in response to HER2 activation.
Main Methods:
- Immunohistochemical analysis of HER2, p53, and p27 expression in 52 breast tumor specimens.
- Analysis of p53 mutations and p53 protein accumulation.
- In vitro studies using HER2-overexpressing cell lines with varying p53 status, stimulated with heregulin beta1 (HRG).
- Assessment of p53 and p27 expression and subcellular localization post-HRG stimulation.
- Gene transfection experiments to restore wild-type p53 function.
Main Results:
- p27 expression was inversely associated with HER2 but directly associated with p53 status.
- Tumors with p53 protein accumulation showed higher p27 expression (93%) compared to mutated p53 (29%) or wild-type p53 (59%).
- HER2-overexpressing cells stimulated with HRG showed increased p27 protein expression correlating with p53 levels, independent of p27 transcript levels.
- p53-null cells did not exhibit p27 upregulation upon HRG stimulation.
- Restoration of wild-type p53 via transfection re-established p27 upregulation in response to HRG.
Conclusions:
- p53 plays a critical role in upregulating p27 expression following HER2 activation.
- The p53-dependent upregulation of p27 may influence therapeutic responses, particularly to Transtuzumab.
More Related Videos
Related Concept Videos
01:19Interactions Between Signaling Pathways
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
02:23Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
01:23Negative Regulator Molecules
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
01:22PI3K/mTOR/AKT Signaling Pathway
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a rapamycin-insensitive companion...
03:03mTOR Signaling and Cancer Progression
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
02:36DNA Damage can Stall the Cell Cycle
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...