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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
Altered expression of cell cycle regulatory proteins in benign and malignant bone and soft tissue neoplasms
Marilyn M Bui1, Tapan K Bagui, David C Boulware
1Department of Interdisciplinary Oncology, University of South Florida, College of Medicine, Tampa, FL 33612-9497, USA.
Background:
The binding of cyclins to cyclin-dependent kinases regulates cell proliferation. Overexpression of cyclins is believed to deregulate the cell cycle in human tumors. Here the expression of G1 cyclins D1 and D3, and of Ki-67 in a variety of bone and soft tissue sarcomas was assessed as compared to adjacent normal tissue and to a subset of leiomyomas.
Materials And Methods:
Twenty-nine human bone and soft tissue sarcomas were evaluated. Tissue sections from each case were subjected to immunostaining for cyclin D1, cyclin D3 and Ki-67 using the avidin-biotin complex method.
Results:
Cyclin D1 nuclear positivity was detected in 28% of sarcomas and in none of the leiomyomas. Cyclin D3 nuclear positivity was present in 62% of sarcomas and in none of the leiomyomas. Ki-67 nuclear staining was positive in 86% of sarcomas but in only 16% of leiomyomas. In addition, upregulation of cyclin D1 was observed in leiomyosarcomas, pleomorphic sarcomas and gastrointestinal stromal tumors, but not in liposarcomas or osteosarcomas. Cyclin D3, however, was expressed in all of the sarcoma types including 2 out of 5 liposarcomas and 1 out of 4 osteosarcomas. The normal soft tissue adjacent to the tumors when present (10 cases) was negative for cyclin D1 and D3, and expressed Ki-67 in 5% of the cell nuclei. The expression of cyclin D3 was also noted in human sarcoma cell lines (SKLMS, MG63, SaOS-2 and HT1080) by Western blot.
Conclusion:
The higher expression of cyclin D1 and D3 and of Ki-67 in bone and soft tissue sarcomas, as compared to leiomyomas and peritumoral normal soft tissue, suggests that high cyclin expression may contribute to deregulation of the cell cycle in bone and soft tissue tumors. These data suggest a role of cyclins in the process of human sarcomagenesis.
Insights
Cyclin D1 and D3 expression is elevated in bone and soft tissue sarcomas compared to normal tissues and leiomyomas. This suggests cyclins play a role in sarcomagenesis and cell cycle deregulation in these tumors.
Area of Science:
- Oncology
- Cell Biology
- Molecular Pathology
Background:
- Cell proliferation is regulated by cyclin binding to cyclin-dependent kinases.
- Overexpression of cyclins is implicated in deregulating the cell cycle in human tumors.
Purpose of the Study:
- To assess the expression of G1 cyclins (D1 and D3) and Ki-67 in bone and soft tissue sarcomas.
- To compare cyclin and Ki-67 expression in sarcomas with adjacent normal tissue and leiomyomas.
Main Methods:
- Immunohistochemical analysis of cyclin D1, cyclin D3, and Ki-67 on 29 human bone and soft tissue sarcomas.
- Comparison with adjacent normal tissues and leiomyomas.
- Western blot analysis of cyclin D3 in human sarcoma cell lines.
Main Results:
- Cyclin D1 nuclear positivity in 28% of sarcomas, absent in leiomyomas.
- Cyclin D3 nuclear positivity in 62% of sarcomas, absent in leiomyomas.
- Ki-67 nuclear staining positive in 86% of sarcomas vs. 16% of leiomyomas.
- Upregulation of cyclin D1 and D3 observed across various sarcoma types, with differential expression patterns.
- Normal adjacent tissues were negative for cyclins D1/D3 and showed low Ki-67 expression.
Conclusions:
- Elevated expression of cyclin D1, D3, and Ki-67 in sarcomas suggests a role in cell cycle deregulation.
- These findings indicate cyclins may contribute to human sarcomagenesis.
- Cyclin expression patterns could be relevant for understanding tumor development.
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