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Heterotypic Three-dimensional In Vitro Modeling of Stromal-Epithelial Interactions During Ovarian Cancer Initiation and Progression
Published on: August 28, 2012
Molecular mechanisms of isocyanate induced oncogenic transformation in ovarian epithelial cells
Gorantla Venkata Raghuram1, Neelam Pathak, Deepika Jain
1Bhopal Memorial Hospital & Research Centre, Bhopal, India.
Abstract:
Ovarian surface epithelium is under constant physiological pressure to maintain its integrity. Environmental toxic exposure can contribute to degenerative pathologies including ovarian cancer. Based on our current understanding, we aimed at listing mechanistic insights that contribute to ovarian carcinogenesis after exposure to methyl isocyanate, an ubiquitous environmental pollutant. Ovarian epithelial cells manifested a persistent DNA damage response along with increased accumulation of GADD45, p21, p16(INK4A) and pRb proteins upon treatment. Increase in cell size and β-gal positive staining showing inception of premature senescence with morphological transformation and structural and numerical chromosomal abnormalities were also observed. Immuno-FISH analysis illustrated early loss of TRF2 protein suggestive of telomeric dysfunction due to premature senescence and plausible association with chromosomal and microsatellite instability. Soft-agar assay displayed neoplasticity in treated cells demonstrating onset of malignant transformation. These results indicate that isocyanate exposure alters ovarian epithelial cell proliferation and might lead to ovarian dysfunction and carcinogenesis.
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