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Published on: February 9, 2024
Downregulation of genes encoding for subunits of adaptor complex-3 in cervical carcinomas
A A Petrenko1, L S Pavlova, A I Karseladze
1Institute of Carcinogenesis, N. N. Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences, Moscow, 115478, Russia.
Abstract:
We explored the expression of four genes encoding for subunits of AP-3 in cervical tumors and cancer cell lines. Using RT-PCR we demonstrated more than twofold decrease in the levels of mRNA of AP3D1, AP3B1, AP3M1, and AP3S1 in 32, 28, 23, and 26% tumors in comparison with normal tissues of uterine cervix, respectively. The level of mRNA of at least one subunit was decreased in 28 out of 47 (60%) of tumors and in four out of five cancer cell lines in comparison to tissues adjacent to tumors. The suppression of expression of any of the subunits was revealed in 15 out of 28 cases (54%). The expression of two and more subunits was decreased simultaneously in different combinations in 13 cases (46%). This fact testifies to the lack of a common mechanism of downregulation of four subunits in tumors. There is a tendency to more frequent suppression of AP-3A expression in tumors associated with lymphatic node metastases as compared with tumors without metastases (P = 0.034). Thus, here we demonstrate for the first time the decrease in expression of genes encoding for AP-3A subunits in tumors.
Insights
This study reveals reduced expression of AP-3 (adaptor protein complex 3) subunits in cervical tumors. This finding highlights potential molecular changes in cervical cancer progression and may offer new diagnostic avenues.
Area of Science:
- Molecular Biology
- Oncology
- Cell Biology
Background:
- Adaptor protein complex 3 (AP-3) plays crucial roles in intracellular trafficking.
- Dysregulation of protein complexes is implicated in various cancers, including cervical cancer.
Purpose of the Study:
- To investigate the expression levels of AP-3 subunits in cervical tumors and cancer cell lines.
- To determine if AP-3 subunit expression is altered in cervical cancer compared to normal tissues.
Main Methods:
- Reverse transcription polymerase chain reaction (RT-PCR) was used to quantify mRNA levels of AP-3 subunits (AP3D1, AP3B1, AP3M1, AP3S1).
- Gene expression was compared between cervical tumor samples, adjacent normal tissues, and cervical cancer cell lines.
Main Results:
- A significant decrease in mRNA levels for AP3D1, AP3B1, AP3M1, and AP3S1 was observed in 32%, 28%, 23%, and 26% of tumors, respectively.
- At least one AP-3 subunit mRNA level was reduced in 60% of tumors and four out of five cancer cell lines.
- Suppression of multiple AP-3 subunits occurred in 46% of tumors, suggesting diverse downregulation mechanisms.
- AP-3A expression showed a trend towards more frequent suppression in tumors with lymphatic node metastasis (P = 0.034).
Conclusions:
- This study provides the first evidence of decreased expression of AP-3A subunits in cervical tumors.
- Altered AP-3 subunit expression may be a feature of cervical carcinogenesis.
- The findings suggest potential roles for AP-3 in cervical cancer development and metastasis.
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