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Ionizing radiation induces heritable disruption of epithelial cell interactions
Catherine C Park1, Rhonda L Henshall-Powell, Anna C Erickson
1Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
Summary
Ionizing radiation (IR) exposure can disrupt normal cell interactions, leading to compromised tissue architecture and polarity in human mammary epithelial cells (HMEC). This non-mutational effect contributes to breast cancer development by altering cell organization.
Area of Science:
- Cell Biology
- Cancer Research
- Radiation Biology
Background:
- Ionizing radiation (IR) is a known human breast carcinogen.
- While mutagenicity is a known mechanism, IR also affects growth factors and extracellular matrix.
- Normal cell interactions may be disrupted by IR, contributing to carcinogenesis.
Purpose of the Study:
- To investigate if IR affects the tissue-specific morphogenesis of nonmalignant human mammary epithelial cells (HMEC) in culture.
- To determine if IR induces non-mutational changes in cell polarity and communication.
Main Methods:
- Confocal microscopy and imaging bioinformatics were used to analyze HMEC.
- Quantification of E-cadherin, beta-catenin, and connexin-43 localization in irradiated HMEC colonies.
- Image analysis to assess acinar organization and cell-extracellular matrix interactions.
Main Results:
- Irradiated HMEC colonies showed decreased localization of E-cadherin, beta-catenin, and connexin-43.
- Majority of irradiated HMEC progeny exhibited severely compromised acinar organization.
- Disrupted cell-cell communication and aberrant cell-extracellular matrix interactions were observed.
Conclusions:
- IR exposure can compromise cell polarity and multicellular organization in HMEC through a heritable, non-mutational mechanism.
- Disrupted tissue architecture and cell interactions in HMEC progeny resemble neoplastic progression.
- These findings suggest a novel pathway for IR-induced carcinogenesis beyond direct DNA damage.