AKT1 Transcriptomic Landscape in Breast Cancer Cells
Overexpression and hyperactivation of the serine/threonine protein kinase B (AKT) pathway is one of the most common cellular events in breast cancer progression. However, the nature of AKT1-specific genome-wide transcriptomic alterations in breast cancer cells and breast cancer remains unknown to th...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-07-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/15/2290 |
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| author | Bijesh George Bin Gui Rajeswari Raguraman Aswathy Mary Paul Harikrishna Nakshatri Madhavan Radhakrishna Pillai Rakesh Kumar |
| author_facet | Bijesh George Bin Gui Rajeswari Raguraman Aswathy Mary Paul Harikrishna Nakshatri Madhavan Radhakrishna Pillai Rakesh Kumar |
| author_sort | Bijesh George |
| collection | DOAJ |
| description | Overexpression and hyperactivation of the serine/threonine protein kinase B (AKT) pathway is one of the most common cellular events in breast cancer progression. However, the nature of AKT1-specific genome-wide transcriptomic alterations in breast cancer cells and breast cancer remains unknown to this point. Here, we delineate the impact of selective AKT1 knock down using gene-specific siRNAs or inhibiting the AKT activity with a pan-AKT inhibitor VIII on the nature of transcriptomic changes in breast cancer cells using the genome-wide RNA-sequencing analysis. We found that changes in the cellular levels of AKT1 lead to changes in the levels of a set of differentially expressed genes and, in turn, imply resulting AKT1 cellular functions. In addition to an expected positive relationship between the status of AKT1 and co-expressed cellular genes, our study unexpectedly discovered an inherent role of AKT1 in inhibiting the expression of a subset of genes in both unstimulated and growth factor stimulated breast cancer cells. We found that depletion of AKT1 leads to upregulation of a subset of genes—many of which are also found to be downregulated in breast tumors with elevated high AKT1 as well as upregulated in breast tumors with no detectable AKT expression. Representative experimental validation studies in two breast cancer cell lines showed a reasonable concurrence between the expression data from the RNA-sequencing and qRT-PCR or data from ex vivo inhibition of AKT1 activity in cancer patient-derived cells. In brief, findings presented here provide a resource for further understanding of AKT1-dependent modulation of gene expression in breast cancer cells and broaden the scope and significance of AKT1 targets and their functions. |
| first_indexed | 2024-03-09T05:32:49Z |
| format | Article |
| id | doaj.art-f83a6406e95a49388f6a3a2d737d73ec |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T05:32:49Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-f83a6406e95a49388f6a3a2d737d73ec2023-12-03T12:31:55ZengMDPI AGCells2073-44092022-07-011115229010.3390/cells11152290AKT1 Transcriptomic Landscape in Breast Cancer CellsBijesh George0Bin Gui1Rajeswari Raguraman2Aswathy Mary Paul3Harikrishna Nakshatri4Madhavan Radhakrishna Pillai5Rakesh Kumar6Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Trivandrum 695014, IndiaBiological Sciences, Ribon Therapeutics, Inc., Cambridge, MA 02140, USACancer Research Program, Rajiv Gandhi Centre for Biotechnology, Trivandrum 695014, IndiaCancer Research Program, Rajiv Gandhi Centre for Biotechnology, Trivandrum 695014, IndiaDepartment of Surgery, Indiana University of School of Medicine, Indianapolis, IN 46202, USACancer Research Program, Rajiv Gandhi Centre for Biotechnology, Trivandrum 695014, IndiaCancer Research Program, Rajiv Gandhi Centre for Biotechnology, Trivandrum 695014, IndiaOverexpression and hyperactivation of the serine/threonine protein kinase B (AKT) pathway is one of the most common cellular events in breast cancer progression. However, the nature of AKT1-specific genome-wide transcriptomic alterations in breast cancer cells and breast cancer remains unknown to this point. Here, we delineate the impact of selective AKT1 knock down using gene-specific siRNAs or inhibiting the AKT activity with a pan-AKT inhibitor VIII on the nature of transcriptomic changes in breast cancer cells using the genome-wide RNA-sequencing analysis. We found that changes in the cellular levels of AKT1 lead to changes in the levels of a set of differentially expressed genes and, in turn, imply resulting AKT1 cellular functions. In addition to an expected positive relationship between the status of AKT1 and co-expressed cellular genes, our study unexpectedly discovered an inherent role of AKT1 in inhibiting the expression of a subset of genes in both unstimulated and growth factor stimulated breast cancer cells. We found that depletion of AKT1 leads to upregulation of a subset of genes—many of which are also found to be downregulated in breast tumors with elevated high AKT1 as well as upregulated in breast tumors with no detectable AKT expression. Representative experimental validation studies in two breast cancer cell lines showed a reasonable concurrence between the expression data from the RNA-sequencing and qRT-PCR or data from ex vivo inhibition of AKT1 activity in cancer patient-derived cells. In brief, findings presented here provide a resource for further understanding of AKT1-dependent modulation of gene expression in breast cancer cells and broaden the scope and significance of AKT1 targets and their functions.https://www.mdpi.com/2073-4409/11/15/2290breast cancerAKT1RNA-sequencingtranscriptomeemerging functions and targetscancer therapeutics |
| spellingShingle | Bijesh George Bin Gui Rajeswari Raguraman Aswathy Mary Paul Harikrishna Nakshatri Madhavan Radhakrishna Pillai Rakesh Kumar AKT1 Transcriptomic Landscape in Breast Cancer Cells Cells breast cancer AKT1 RNA-sequencing transcriptome emerging functions and targets cancer therapeutics |
| title | AKT1 Transcriptomic Landscape in Breast Cancer Cells |
| title_full | AKT1 Transcriptomic Landscape in Breast Cancer Cells |
| title_fullStr | AKT1 Transcriptomic Landscape in Breast Cancer Cells |
| title_full_unstemmed | AKT1 Transcriptomic Landscape in Breast Cancer Cells |
| title_short | AKT1 Transcriptomic Landscape in Breast Cancer Cells |
| title_sort | akt1 transcriptomic landscape in breast cancer cells |
| topic | breast cancer AKT1 RNA-sequencing transcriptome emerging functions and targets cancer therapeutics |
| url | https://www.mdpi.com/2073-4409/11/15/2290 |
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