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Loss of USF transcriptional activity in breast cancer cell lines
1Department of Molecular Genetics, University of Texas M. D. Anderson Cancer Center, Houston, Texas, TX 77030, USA.
Abstract:
USF is a family of transcription factors that are structurally related to the Myc oncoproteins and also share with Myc a common DNA-binding specificity. USF overexpression can prevent c-Myc-dependent cellular transformation and also inhibit the proliferation of certain transformed cells. These antiproliferative activities suggest that USF inactivation could be implicated in carcinogenesis. To explore this possibility, we compared the activities of the ubiquitous USF1 and USF2 proteins in several cell lines derived from either normal breast epithelium or breast tumors. The DNA-binding activities of USF1 and USF2 were present at similar levels in all cell lines. In the non-tumorigenic MCF-10A cells, USF in general, and USF2 in particular, exhibited strong transcriptional activities. In contrast, USF1 and USF2 were completely inactive in three out of six transformed breast cell lines investigated, while the other three transformed cell lines exhibited loss of USF2 activity. Analyses in cells cultured from healthy tissue confirmed the transcriptional activity of USF in normal human mammary epithelial cells. These results demonstrate that a partial or complete loss of USF function is a common event in breast cancer cell lines, perhaps because, like Myc overexpression, it favors rapid proliferation.
Insights
Loss of USF transcription factor function is common in breast cancer cell lines. This inactivation may promote rapid cell proliferation, contributing to carcinogenesis.
Area of Science:
- Molecular Biology
- Cancer Research
- Cellular Biology
Background:
- Upstream transcription factor (USF) proteins are structurally similar to Myc oncoproteins.
- USF overexpression inhibits cellular transformation and proliferation, suggesting a role in preventing cancer.
- USF inactivation may be implicated in carcinogenesis.
Purpose of the Study:
- To investigate the role of USF1 and USF2 in breast cancer.
- To compare USF activity in normal breast epithelial cells versus breast tumor cell lines.
Main Methods:
- Comparison of USF1 and USF2 DNA-binding and transcriptional activities.
- Analysis of USF function in normal (MCF-10A) and malignant breast cell lines.
- Examination of USF activity in primary human mammary epithelial cells.
Main Results:
- USF1 and USF2 DNA-binding activities were consistent across all cell lines.
- USF proteins, particularly USF2, showed strong transcriptional activity in normal MCF-10A cells.
- Three of six breast cancer cell lines displayed complete USF1 and USF2 inactivity, while the others showed loss of USF2 activity.
- Normal human mammary epithelial cells confirmed USF transcriptional activity.
Conclusions:
- A partial or complete loss of USF function is a frequent occurrence in breast cancer cell lines.
- USF inactivation may facilitate uncontrolled cell proliferation, similar to Myc overexpression.
- USF dysfunction is potentially linked to the development of breast cancer.