Deep proteome profiling of human mammary epithelia at lineage and age resolution
Summary: Age is the major risk factor in most carcinomas, yet little is known about how proteomes change with age in any human epithelium. We present comprehensive proteomes comprised of >9,000 total proteins and >15,000 phosphopeptides from normal primary human mammary epithelia at lineage re...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2021-09-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004221009949 |
| _version_ | 1818600447853723648 |
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| author | Stefan Hinz Antigoni Manousopoulou Masaru Miyano Rosalyn W. Sayaman Kristina Y. Aguilera Michael E. Todhunter Jennifer C. Lopez Lydia L. Sohn Leo D. Wang Mark A. LaBarge |
| author_facet | Stefan Hinz Antigoni Manousopoulou Masaru Miyano Rosalyn W. Sayaman Kristina Y. Aguilera Michael E. Todhunter Jennifer C. Lopez Lydia L. Sohn Leo D. Wang Mark A. LaBarge |
| author_sort | Stefan Hinz |
| collection | DOAJ |
| description | Summary: Age is the major risk factor in most carcinomas, yet little is known about how proteomes change with age in any human epithelium. We present comprehensive proteomes comprised of >9,000 total proteins and >15,000 phosphopeptides from normal primary human mammary epithelia at lineage resolution from ten women ranging in age from 19 to 68 years. Data were quality controlled and results were biologically validated with cell-based assays. Age-dependent protein signatures were identified using differential expression analyses and weighted protein co-expression network analyses. Upregulation of basal markers in luminal cells, including KRT14 and AXL, were a prominent consequence of aging. PEAK1 was identified as an age-dependent signaling kinase in luminal cells, which revealed a potential age-dependent vulnerability for targeted ablation. Correlation analyses between transcriptome and proteome revealed age-associated loss of proteostasis regulation. Age-dependent proteome changes in the breast epithelium identified heretofore unknown potential therapeutic targets for reducing breast cancer susceptibility. |
| first_indexed | 2024-12-16T12:35:38Z |
| format | Article |
| id | doaj.art-e72f584687ea4298b6399b8a51b8f7ce |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-16T12:35:38Z |
| publishDate | 2021-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-e72f584687ea4298b6399b8a51b8f7ce2022-12-21T22:31:35ZengElsevieriScience2589-00422021-09-01249103026Deep proteome profiling of human mammary epithelia at lineage and age resolutionStefan Hinz0Antigoni Manousopoulou1Masaru Miyano2Rosalyn W. Sayaman3Kristina Y. Aguilera4Michael E. Todhunter5Jennifer C. Lopez6Lydia L. Sohn7Leo D. Wang8Mark A. LaBarge9Department of Population Sciences, Beckman Research Institute, Duarte, USADepartments of Pediatrics and ImmunoOncology, City of Hope, 1500 E. Duarte Rd, Duarte, CA 91010, USADepartment of Population Sciences, Beckman Research Institute, Duarte, USADepartment of Population Sciences, Beckman Research Institute, Duarte, USA; Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94143, USADepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USADepartment of Population Sciences, Beckman Research Institute, Duarte, USADepartment of Population Sciences, Beckman Research Institute, Duarte, USADepartment of Mechanical Engineering, University of California at Berkeley, Berkeley 94720-1740, USADepartments of Pediatrics and ImmunoOncology, City of Hope, 1500 E. Duarte Rd, Duarte, CA 91010, USA; Corresponding authorDepartment of Population Sciences, Beckman Research Institute, Duarte, USA; Center for Cancer and Aging Research, Duarte, USA; Corresponding authorSummary: Age is the major risk factor in most carcinomas, yet little is known about how proteomes change with age in any human epithelium. We present comprehensive proteomes comprised of >9,000 total proteins and >15,000 phosphopeptides from normal primary human mammary epithelia at lineage resolution from ten women ranging in age from 19 to 68 years. Data were quality controlled and results were biologically validated with cell-based assays. Age-dependent protein signatures were identified using differential expression analyses and weighted protein co-expression network analyses. Upregulation of basal markers in luminal cells, including KRT14 and AXL, were a prominent consequence of aging. PEAK1 was identified as an age-dependent signaling kinase in luminal cells, which revealed a potential age-dependent vulnerability for targeted ablation. Correlation analyses between transcriptome and proteome revealed age-associated loss of proteostasis regulation. Age-dependent proteome changes in the breast epithelium identified heretofore unknown potential therapeutic targets for reducing breast cancer susceptibility.http://www.sciencedirect.com/science/article/pii/S2589004221009949Developmental biologyComplex system biologyProteomics |
| spellingShingle | Stefan Hinz Antigoni Manousopoulou Masaru Miyano Rosalyn W. Sayaman Kristina Y. Aguilera Michael E. Todhunter Jennifer C. Lopez Lydia L. Sohn Leo D. Wang Mark A. LaBarge Deep proteome profiling of human mammary epithelia at lineage and age resolution iScience Developmental biology Complex system biology Proteomics |
| title | Deep proteome profiling of human mammary epithelia at lineage and age resolution |
| title_full | Deep proteome profiling of human mammary epithelia at lineage and age resolution |
| title_fullStr | Deep proteome profiling of human mammary epithelia at lineage and age resolution |
| title_full_unstemmed | Deep proteome profiling of human mammary epithelia at lineage and age resolution |
| title_short | Deep proteome profiling of human mammary epithelia at lineage and age resolution |
| title_sort | deep proteome profiling of human mammary epithelia at lineage and age resolution |
| topic | Developmental biology Complex system biology Proteomics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004221009949 |
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