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The interplay of PTEN and AKT nexus in breast cancer: a molecular perspective
Anum Kamal1,2, Ali Raza Awan2, Masood Rabbani3
1Lahore Garrison University, Lahore, Pakistan.
Background:
Breast cancer is a highly prevalent and life-threatening ailment that is commonly detected among the females. The downregulation of PTEN in breast cancer is associated with a poor prognosis, aggressive tumor type, and metastasis to lymph nodes, as it activates the pro-survival pathway PI3K/AKT, which is considered the ultimate proliferative pathway.
Material And Methods:
The mRNA expression of PTEN and AKT genes was investigated using RT-qPCR and TaqMan primer probe chemistry. Moreover DNA was also isolated from the same tissue samples and exonic regions of both genes were amplified for mutational analysis. The proteins expression of PTEN and AKT from seven human breast cancer cell lines was checked through western blot experiments.
Result:
The study revealed a decrease in PTEN expression in 73.3% of the samples, whereas an increase in AKT expression in 40% of samples was observed when compared to the distant normal breast tissue. Conversely, the remaining 60% of samples exhibited a decrease in AKT mRNA expression. There was no observed alteration in the genetic sequence of AKT and PTEN within the targeted amplified regions of breast cancer samples. The high levels of PTEN protein in T-47D and MDA-MB-453 resulted in a lower p-AKT. Two cell lines ZR-75-1 and MDA-MB-468 appeared to be PTEN negative on western blot but mRNA was detected on RT-qPCR.
Conclusion:
In breast cancer the status/expression of PTEN & AKT at mRNA and protein level might be obliging in forecasting the path of disease progression, treatment and prognosis.
Insights
Reduced PTEN and altered AKT expression in breast cancer may predict disease progression. This study investigated PTEN and AKT gene and protein levels in breast cancer tissues and cell lines.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Breast cancer is a common and dangerous disease in women.
- Decreased PTEN (Phosphatase and tensin homolog) expression in breast cancer correlates with poor prognosis and metastasis.
- PTEN normally inhibits the PI3K/AKT pathway, a key driver of cell proliferation.
Purpose of the Study:
- To investigate the mRNA and protein expression of PTEN and AKT in breast cancer.
- To analyze potential mutations in PTEN and AKT genes.
- To explore the relationship between PTEN and AKT expression and breast cancer progression.
Main Methods:
- Quantitative reverse transcription PCR (RT-qPCR) was used to measure PTEN and AKT mRNA levels.
- DNA was isolated for mutational analysis of exonic regions of PTEN and AKT.
- Western blotting was performed to assess PTEN and AKT protein expression in seven breast cancer cell lines.
Main Results:
- PTEN expression was decreased in 73.3% of breast cancer samples compared to normal tissue.
- AKT mRNA expression increased in 40% of samples, while 60% showed decreased expression.
- No mutations were found in the analyzed regions of PTEN and AKT genes; high PTEN protein correlated with lower p-AKT.
Conclusions:
- PTEN and AKT expression levels at both mRNA and protein levels may be crucial for predicting breast cancer disease progression.
- The findings suggest PTEN and AKT status can inform treatment strategies and prognosis for breast cancer patients.
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