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Published on: February 9, 2024
Downregulation of calcineurin activity in cervical carcinoma
S Padma1, A Pavani Sowjanya, Usha Rani Poli
1Centre for DNA Fingerprinting and Diagnostics, Nacharam, Hyderabad, A,P, India. gayatri@cdfd.org.in.
Abstract:
BACKGROUND: Calcineurin (CaN) is an important serine-threonine phosphatase (PP2B), which plays a crucial role in calcium-calmodulin mediated signal transduction events. Calcineurin has been implicated in pathogenesis of various diseases cardiac hypertrophy, diabetic neuropathy and Alzheimer's, however its role in neoplasia remains unclear. RESULTS: In view of this we evaluated the calcineurin activity in serum and biopsy samples collected from women diagnosed with invasive squamous cell carcinoma of cervix. A significant reduction was observed in the calcineurin activity in cancer cervix patients compared to the control group. However the calcineurin activity remained unaltered in the cervical scrapes obtained from patients diagnosed with low-grade squamous intra epithelial lesions (LSIL). Interestingly the downregulation of calcineurin activity in squamous cell carcinomas was not accompanied by any significant change in DNA-binding affinity of the transcriptional factor NFAT (Nuclear Factor of Activated T-cells). All the squamous cell carcinoma samples used in the present study were positive for high-risk human papillomavirus (HPV) types. CONCLUSION: The present study demonstrates the downregulation of calcineurin activity in squamous cell carcinoma of cervix with high risk HPV infection. We conclude that perturbations in calcineurin-mediated pathway may be involved in development of cervical neoplasia.
Insights
Calcineurin (CaN) activity is significantly reduced in cervical cancer patients with high-risk HPV infection. This finding suggests that altered calcineurin pathways may contribute to the development of cervical neoplasia.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Calcineurin (CaN), a serine-threonine phosphatase (PP2B), is vital in calcium-calmodulin signaling.
- While implicated in diseases like cardiac hypertrophy and Alzheimer's, CaN's role in neoplasia is not well understood.
Purpose of the Study:
- To investigate calcineurin activity in cervical cancer.
- To explore the relationship between calcineurin activity, HPV infection, and cervical neoplasia.
Main Methods:
- Assessed calcineurin activity in serum and biopsy samples from cervical cancer patients and controls.
- Analyzed calcineurin activity in cervical scrapes from patients with low-grade squamous intraepithelial lesions (LSIL).
- Evaluated the DNA-binding affinity of the transcription factor NFAT (Nuclear Factor of Activated T-cells).
Main Results:
- Significantly reduced calcineurin activity was observed in cervical cancer patients compared to controls.
- Calcineurin activity remained unchanged in LSIL cases.
- Downregulation of calcineurin in squamous cell carcinomas did not affect NFAT DNA-binding affinity.
- All cervical squamous cell carcinoma samples were positive for high-risk human papillomavirus (HPV) types.
Conclusions:
- Calcineurin activity is downregulated in cervical squamous cell carcinoma associated with high-risk HPV.
- Perturbations in calcineurin-mediated pathways may play a role in cervical neoplasia development.
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