Inhibition of cyclic AMP-triggered aromatase gene expression in human choriocarcinoma cells by antisense oligodeoxynucleotide

Area of Science:

• Biochemistry
• Molecular Biology
• Oncology

Background:

• Aromatase is the key enzyme in estrogen biosynthesis, crucial for estrogen-dependent tumor growth.
• Current aromatase inhibitors are vital therapeutic tools, but enhanced specificity is desired.

Purpose of the Study:

• To investigate the efficacy of inhibiting aromatase gene expression at the nucleic acid level using an antisense approach.
• To evaluate the potential of antisense oligodeoxynucleotides as specific aromatase inhibitors.

Main Methods:

• Synthesis of an antisense oligodeoxynucleotide (antisense-arom) targeting the translation start region of human aromatase transcripts.
• Application of antisense-arom to inhibit cyclic AMP-triggered aromatase gene expression in JEG-3 cells (human choriocarcinoma cell line).
• Assessment of aromatase mRNA levels, protein expression, and enzyme activity following antisense treatment.

Main Results:

• Significant inhibition of aromatase gene expression (70% and 60%) was achieved under both autocrine and induced conditions.
• Antisense-arom treatment accelerated aromatase mRNA degradation.
• A decrease in aromatase protein and microsomal activity was observed, correlating with nucleic acid inhibition.

Conclusions:

• The antisense strategy demonstrates a highly promising approach for developing novel, specific aromatase inhibitors.
• Targeting aromatase at the nucleic acid level offers a new therapeutic avenue for estrogen-dependent cancers.