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| Status |
Public on Apr 26, 2016 |
| Title |
Effect of pubertal BPA exposure on mammary stem cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Perinatal exposure to bisphenol A (BPA) has been shown to cause aberrant mammary gland morphogenesis and mammary neoplastic transformation. Yet, the underlying mechanism is poorly understood. We tested the hypothesis that mammary glands exposed to BPA during a susceptible window may lead to its susceptibility to tumorigenesis through a stem-cell mediated mechanism. We exposed 21-day-old Balb/c mice to BPA by gavage (25 µg/kg/day) during puberty for 3 weeks, and a subset of animals were further challenged with one oral dose (30 mg/kg) of 7,12-dimethylbenz[a]anthracene (DMBA) at 2 months of age. Primary mammary cells were isolated at 6 weeks, and 2 and 4 months of age for mammary stem cell (MaSC) quantification and function analysis. Pubertal exposure to the low-dose BPA increased lateral branches and hyperplasia in adult mammary glands and caused an acute increase of MaSC in 6-week-old glands and a delayed increase of luminal progenitors in 4-month-old adult gland. Most importantly, pubertal BPA exposure altered the function of MaSC from different age groups, causing pre-neoplastic lesions in their regenerated glands similar to those induced by DMBA exposure, which indicates that MaSCs are susceptible to BPA-induced transformation. Deep sequencing analysis on MaSC-enriched mammospheres identified a set of aberrantly expressed genes associated with pre-neoplastic lesions in human breast cancer patients. Thus, our study for the first time shows that pubertal BPA exposure altered MaSC gene expression and function such that they induced early neoplastic transformation.
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| Overall design |
Four samples were analyzed (control, BPA, DMBA, BPA+DMBA), and for each treatment group, mammospheres from 5 animals were pooled for RNA extraction.
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| Contributor(s) |
Dong Q, Sun LZ |
| Citation(s) |
24520039 |
| Submission date |
May 09, 2013 |
| Last update date |
May 15, 2019 |
| Contact name |
Yidong Chen |
| E-mail(s) |
cheny8@uthscsa.edu
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| Phone |
2105629163
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| Organization name |
UT Health Science Center at San Antonio
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| Department |
Population Health Sciences
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| Street address |
8403 Floyd Curl Drive, MSC 7784
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| City |
San Antonio |
| State/province |
Texas |
| ZIP/Postal code |
78229 |
| Country |
USA |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA202390 |
| SRA |
SRP022252 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE46815_RAW.tar |
390.0 Kb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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