Generation of Immortalised But Unstable Cells after hTERT Introduction in Telomere-Compromised and p53-Deficient vHMECs

International Journal of Molecular Sciences
Aina BernalLaura Tusell

Abstract

Telomeres, the natural ends of chromosomes, hide the linear telomeric DNA from constitutive exposure to the DNA damage response with a lariat structure or t-loop. Progressive telomere shortening associated with DNA replication in the absence of a compensatory mechanism culminates in t-loop collapse and unmasked telomeres. Dysfunctional telomeres can suppress cancer development by engaging replicative senescence or apoptosis, but they can also promote tumour initiation when cell cycle checkpoints are disabled. In this setting, telomere dysfunction promotes increasing chromosome instability (CIN) through breakage-fusion-bridge cycles. Excessive instability may hamper cell proliferation but might allow for the appearance of some rare advantageous mutations that could be selected and ultimately favour neoplastic progression. With the aim of generating pre-malignant immortalised cells, we ectopically expressed telomerase in telomere-compromised variant human mammary epithelial cells (vHMECs), proficient and deficient for p53, and analysed structural and numerical chromosomal aberrations as well as abnormal nuclear morphologies. Importantly, this study provides evidence that while immortalisation of vHMECs at early stages results in ...Continue Reading

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Methods Mentioned

BETA
genetic modifications
FACS
chromosomal aberration
chromosomal aberrations
Transfection
Fluorescence

Software Mentioned

Chemidoc
GraphPad
Quantity One
GraphPad Prism
Cytovision

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