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Updated: Sep 26, 2026
Transfer of Mammary Gland-forming Ability Between Mammary Basal Epithelial Cells and Mammary Luminal Cells via Extracellular Vesicles/Exosomes
Published on: June 3, 2017
Growth control of mouse mammary epithelial cells by keratin antibody-targeted liposome containing oligonucleotides
In-Suh Yuh1, Seung-Youp Lee, Byong-Ju Hong
1Department of Dairy Science, College of Animal Resources Sciences, Kangwon National University, Hyozadong, Chuncheon, Republic of Korea 200-701. insuhyuh@kangwon.ac.kr
Abstract:
NMuMG cells were incubated with 17beta-estradiol (E)+progesterone (P)+epidermal growth factor (EGF), with or without various types of oligomers (21-mers) to the EGF receptor activity domain (amino acid residues 718 to 724). Sense or antisense oligomers were encapsulated in protein A-bearing liposomes. Uncoupled protein A and unencapsulated sense or antisense oligomers were separated from liposomes on a Sepharose 4B column (the encapsulation efficiency of oligomers in liposome-protein A was 0.8%). The addition of various concentrations of EGF to E+P showed an interaction between them during DNA synthesis (P<0.05). Antisense oligomers (1 microM) decreased DNA synthesis induced by E+P+EGF (65.0% inhibition, P<0.05). Sense oligomers also inhibited DNA synthesis induced by E+P+EGF (P<0.05). However, random-sequence oligomers did not inhibit EGF-induced DNA synthesis. We cannot rule out the possibility that sense oligomers match an unknown functional gene mRNA involved in cell growth, which causes their inhibitory effect. Cells were incubated with a keratin monoclonal antibody and then with dilutions of protein A-bound liposomes containing sense or antisense oligomers in the presence of E+P+EGF. Dose dependent inhibition of DNA synthesis was observed. The encapsulated oligomers in protein A-bound liposomes inhibited DNA synthesis at a 100-fold lower concentration than that of unencapsulated oligomers or the oligomer+liposome mixture. The tyrosine kinase activity domain has an important role in EGF regulation of mammary growth. The effect of a cytokeratin-targeted antibody on DNA synthesis in normal mouse mammary epithelial cells was marginal.
Insights
Antisense oligomers targeting the epidermal growth factor (EGF) receptor significantly inhibited EGF-induced DNA synthesis in mammary cells. Encapsulated oligomers were more potent, highlighting the receptor
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Epidermal growth factor (EGF) plays a crucial role in regulating mammary gland growth and epithelial cell proliferation.
- Understanding the specific domains and mechanisms of EGF receptor (EGFR) signaling is vital for comprehending mammary development and potential therapeutic interventions.
Purpose of the Study:
- To investigate the role of the epidermal growth factor receptor (EGFR) activity domain in EGF-mediated DNA synthesis in NMuMG cells.
- To evaluate the efficacy of antisense and sense oligomers targeting the EGFR activity domain in modulating EGF-induced mammary cell proliferation.
Main Methods:
- NMuMG cells were treated with 17beta-estradiol (E), progesterone (P), and EGF, with or without encapsulated oligomers targeting the EGFR activity domain (residues 718-724).
- Oligomers were encapsulated in protein A-bearing liposomes to enhance delivery and cellular uptake.
- DNA synthesis was measured to assess the impact of EGF and oligomer treatments.
Main Results:
- EGF significantly interacted with E+P to stimulate DNA synthesis in NMuMG cells (P<0.05).
- Antisense oligomers (1 microM) targeting the EGFR activity domain inhibited EGF-induced DNA synthesis by 65.0% (P<0.05).
- Sense oligomers also demonstrated inhibitory effects, while random-sequence oligomers did not, suggesting sequence-specific activity. Encapsulated oligomers were 100-fold more potent than unencapsulated ones.
Conclusions:
- The tyrosine kinase activity domain of the EGF receptor is critical for EGF-regulated mammary growth.
- Antisense oligomers targeting this domain effectively inhibit EGF-induced DNA synthesis, demonstrating a potential strategy for modulating mammary cell proliferation.
- Liposomal encapsulation significantly enhances the potency of oligomers in inhibiting EGFR signaling.
