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Differential osmosensing signalling pathways and G-protein involvement in human cervical cells with different tumour
1Department of Obstetrics and Gynecology, National Cheng Kung University Medical College, Tainan, Taiwan.
Abstract:
Previous studies show that the regulatory volume decrease (RVD) in human cervical cells with different tumour potential may be mediated by different ion channels. The signalling events involved in regulating these channel activities are not clear. To screen the possible mechanisms involved in cell volume regulation in these cells, we examine intracellular mechanisms and second messengers listed as follows: phospholipase C (PLC), phospholipase A2 (PLA2), tyrosine kinase (TK), protein kinase C (PKC), protein kinase A (PKA), and cAMP. The involvement of G-protein was also studied. Our results showed that PLC signalling with downstream activation of PKC was involved in the cell volume regulation of cervical cancer cells. On the other hand, different PKC isoforms that were not related to upstream PLC regulation were involved in the RVD of human papillomavirus (HPV)-immortalised and normal cervical epithelia. Furthermore, GTP-gamma S facilitated the process of RVD in cervical cancer cells, while pertussis toxin retarded this process. In contrast, neither GTP-gamma S nor pertussis toxin showed effect on the RVD responses of HPV-immortalised and normal cervical cells.
Insights
Cell volume regulation in cervical cells differs by tumor potential. Phospholipase C (PLC) and protein kinase C (PKC) pathways are key in cancer cells, while other PKC isoforms regulate normal and HPV-immortalized cells.
Area of Science:
- Cell biology
- Molecular signaling
- Cancer research
Background:
- Regulatory volume decrease (RVD) mechanisms vary across human cervical cells with differing tumor potential.
- The specific ion channels and intracellular signaling events governing RVD remain incompletely understood.
Purpose of the Study:
- To investigate the intracellular mechanisms and second messengers involved in cell volume regulation in human cervical cells.
- To differentiate the signaling pathways mediating RVD in normal, HPV-immortalized, and cancerous cervical cells.
Main Methods:
- Screening of intracellular mechanisms including phospholipase C (PLC), phospholipase A2 (PLA2), tyrosine kinase (TK), protein kinase C (PKC), protein kinase A (PKA), and cAMP.
- Assessment of G-protein involvement using GTP-gamma S and pertussis toxin.
Main Results:
- Phospholipase C (PLC) signaling, leading to protein kinase C (PKC) activation, is implicated in the RVD of cervical cancer cells.
- Distinct PKC isoforms, independent of upstream PLC, mediate RVD in human papillomavirus (HPV)-immortalized and normal cervical epithelia.
- G-protein involvement was observed in cervical cancer cells (facilitated by GTP-gamma S, inhibited by pertussis toxin) but not in normal or HPV-immortalized cells.
Conclusions:
- Cell volume regulation in cervical cancer cells involves PLC-dependent PKC signaling and G-protein pathways.
- RVD in normal and HPV-immortalized cervical cells is regulated by alternative PKC isoforms, independent of PLC and G-protein signaling pathways examined.