SUM-52PE Xenograft Model Overview
The SUM-52PE xenograft model is derived from a human breast carcinoma and is a well-established model of HER2-amplified luminal breast cancer. Originally isolated from a pleural effusion of a patient with metastatic breast cancer, the SUM-52PE cell line exhibits robust overexpression of HER2 (ERBB2) in the absence of estrogen receptor (ER) or progesterone receptor (PR) expression. This molecular configuration, while HER2-positive, places the model outside the classic luminal A/B subtypes, making it particularly relevant for studying HER2-driven tumorigenesis independent of hormonal signaling.
The SUM-52PE xenograft exhibits aggressive growth characteristics in vivo and a consistent HER2 amplification signature, making it highly suitable for evaluating HER2-targeted therapies, resistance to trastuzumab and tyrosine kinase inhibitors, and co-targeting strategies involving downstream signaling nodes such as PI3K, AKT, and mTOR. It is also utilized in studies of receptor internalization, recycling, and post-receptor signaling alterations contributing to therapeutic escape.
Request a Custom Quote for SUM-52PE Xenograft ModelBiological and Molecular Characteristics
SUM-52PE cells are characterized by high-level amplification and overexpression of the HER2 oncogene, resulting in constitutive activation of downstream mitogenic pathways. Despite being HER2-positive, the cell line is ER- and PR-negative, aligning it with HER2-enriched molecular subtypes. The cell line harbors activating mutations in the PIK3CA gene and demonstrates persistent phosphorylation of AKT and ERK, both critical for cell survival and proliferation.
The absence of ER and PR expression removes the confounding influence of endocrine signaling, allowing for clearer interpretation of HER2-targeted treatment responses. In addition to HER2 overexpression, SUM-52PE expresses basal markers including cytokeratin 5 and 17, indicating a hybrid molecular phenotype that supports tumor cell plasticity and resistance modeling.
| Characteristic | SUM-52PE Profile |
|---|---|
| Tumor Type | Human breast carcinoma (HER2-amplified) |
| Origin | Pleural effusion, metastatic site |
| Receptor Status | HER2+, ER–, PR– |
| HER2 Amplification | High (ERBB2 copy number gain) |
| PIK3CA Mutation | Present (activating hotspot mutation) |
| Downstream Signaling | p-AKT+, p-ERK+ |
| Basal Markers | CK5+, CK17+ |
| EMT Features | Minimal |
| Proliferation Rate | High (doubling time <36 hrs) |
| PTEN Status | Intact (partial expression) |
This molecular signature makes SUM-52PE ideal for research into HER2-overexpressing, hormone-independent breast tumors, and for dissecting drug resistance mechanisms in a well-controlled receptor context.
In Vivo Model Development and Tumorigenicity
The SUM-52PE xenograft model is established by subcutaneous injection of 5 × 10^6 to 1 × 10^7 cells suspended in a basement membrane matrix (e.g., Matrigel) into immunocompromised mice such as NOD/SCID or athymic nude mice. Tumor take rates typically exceed 90%, with detectable masses forming within 7 to 10 days post-implantation. Endpoint volumes (1,200–1,500 mm³) are usually reached within 4 to 5 weeks, depending on host strain and growth conditions.
Although the model is commonly used in subcutaneous format, it can also be orthotopically implanted into the mammary fat pad to more accurately replicate the breast tumor microenvironment, particularly for experiments involving HER2-driven stromal interactions, vascularization, and drug delivery kinetics.
SUM-52PE tumors retain HER2 amplification in vivo and are amenable to luciferase or fluorescent labeling, allowing for longitudinal imaging studies and early detection of relapse. Their consistent growth and receptor profile support rigorous, reproducible testing of HER2-directed monoclonal antibodies, small molecule inhibitors, and antibody-drug conjugates (ADCs).
Request a Custom Quote for SUM-52PE Xenograft ModelHistopathology and Immunohistochemical Profile
Histologically, SUM-52PE xenografts present as moderately to highly cellular tumors composed of polygonal epithelial cells with prominent nucleoli, moderate nuclear pleomorphism, and occasional mitotic figures. Tumor architecture is typically solid, with focal gland-like or pseudo-lobular structures and minimal necrosis. The stroma is sparse and typically devoid of inflammatory infiltration under untreated conditions.
Immunohistochemistry shows strong, uniform membrane staining for HER2/neu, with absent staining for estrogen and progesterone receptors. Ki-67 proliferation indices typically range from 50–70%, reflecting the model’s rapid in vivo growth. Downstream HER2 signaling is confirmed by phospho-AKT and phospho-ERK staining. PTEN is detectable but variably expressed in subpopulations, potentially contributing to PI3K/AKT axis activation.
The expression of cytokeratin 5/17 alongside HER2 confirms the hybrid basal-HER2 molecular phenotype. These features support use in evaluating signaling divergence and convergence in the context of HER2 amplification and basal cell markers.
Preclinical Applications and Drug Response
The SUM-52PE xenograft model is used extensively in the evaluation of HER2-targeted therapeutics, including trastuzumab, pertuzumab, lapatinib, neratinib, and trastuzumab-emtansine (T-DM1). Its rapid growth and sustained HER2 expression allow for consistent dosing schedules and reproducible pharmacodynamic measurements. The model is particularly valuable for dissecting resistance mechanisms related to receptor internalization, PI3K pathway activation, and downstream signaling escape.
Given its PIK3CA mutation and PI3K/AKT activation, the model is also well suited for testing inhibitors of the PI3K/AKT/mTOR pathway, either alone or in combination with HER2-directed agents. It has also been used to evaluate strategies targeting receptor recycling, lipid raft localization, and ubiquitination of HER2 under therapeutic pressure.
Because of its hormone receptor negativity, the SUM-52PE model is useful for distinguishing HER2-driven effects from those of estrogen signaling and for exploring alternative resistance mechanisms in patients with HER2+/ER– tumors. It is widely utilized in both monotherapy and combination therapy designs and supports testing of both early-phase compounds and late-stage biologics.
Request This Model
To incorporate the SUM-52PE xenograft model into HER2-targeted therapy development, resistance mechanism studies, or combination regimen testing, please use the quote request link below. Both subcutaneous and orthotopic implantation services are supported, along with HER2 IHC validation, pharmacodynamic biomarker profiling, and tumor growth kinetics analysis.
Request a Custom Quote for SUM-52PE Xenograft Model