Membrane estrogen signaling enhances tumorigenesis and metastatic potential of breast cancer cells via estrogen receptor-α36 (ERα36)
| Autor: | Natalia Cuenca, Rene Olivares-Navarrete, Barbara D. Boyan, Zvi Schwartz, Agreen Hadadi, Reyhaan A. Chaudhri |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
medicine.medical_specialty
Estrogen receptor Apoptosis Breast Neoplasms Biology medicine.disease_cause Biochemistry Metastasis Internal medicine Chlorocebus aethiops medicine Animals Estrogen Receptor beta Humans Protein Isoforms Neoplasm Invasiveness Neoplasm Metastasis skin and connective tissue diseases Molecular Biology Estrogen receptor beta Protein Kinase C Cell Proliferation Estradiol Cell growth Cell Membrane Estrogen Receptor alpha Estrogens Molecular Bases of Disease Cell Biology medicine.disease Antibodies Neutralizing Neoplasm Proteins Enzyme Activation Alternative Splicing Endocrinology Cancer cell COS Cells Cancer research Female Signal transduction Carcinogenesis Estrogen receptor alpha HeLa Cells Signal Transduction |
| Zdroj: | The Journal of biological chemistry. 287(10) |
| ISSN: | 1083-351X |
| Popis: | Protein kinase C (PKC) signaling can be activated rapidly by 17β-estradiol (E(2)) via nontraditional signaling in ERα-positive MCF7 and ERα-negative HCC38 breast cancer cells and is associated with tumorigenicity. Additionally, E(2) has been shown to elicit anti-apoptotic effects in cancer cells counteracting pro-apoptotic effects of chemotherapeutics. Supporting evidence suggests the existence of a membrane-associated ER that differs from the traditional receptors, ERα and ERβ. Our aim was to identify the ER responsible for rapid PKC activation and to evaluate downstream effects, such as proliferation, apoptosis, and metastasis. RT-PCR, Western blot, and immunofluorescence were used to determine the presence of ER splice variants in multiple cell lines. E(2) effects on PKC activity were measured with and without ER-blocking antibodies. Cell proliferation was determined by [(3)H]thymidine incorporation, and cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, (MTT) whereas apoptosis was determined by DNA fragmentation and TUNEL. Quantitative RT-PCR and sandwich ELISA were used to determine the effects on metastatic factors. The role of membrane-dependent signaling in cancer cell invasiveness was examined using an in vitro assay. The results indicate the presence of an ERα splice variant, ERα36, in ERα-positive MCF7 and ERα-negative HCC38 breast cancer cells, which localized to plasma membranes and rapidly activated PKC in response to E(2), leading to deleterious effects such as enhancement of proliferation, protection against apoptosis, and enhancement of metastatic factors. These findings propose ERα36 as a novel target for the development of therapies that can prevent progression of breast cancer in the primary tumor as well as during metastasis. |
| Databáze: | OpenAIRE |
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