N-Acetyltransferase 1 Knockout Elevates Acetyl Coenzyme A Levels and Reduces Anchorage-Independent Growth in Human Breast Cancer Cell Lines
Joint Authors
Stepp, Marcus W.
Salazar-González, Raúl A.
Hong, Kyung U.
Doll, Mark A.
Hein, David W.
Source
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-11, 11 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-08-20
Country of Publication
Egypt
No. of Pages
11
Main Subjects
Abstract EN
Elevated expression of N-acetyltransferase 1 (NAT1) is associated with invasive and lobular breast carcinomas as well as with bone metastasis following an epithelial-to-mesenchymal transition.
We investigated the effect of NAT1 gene deletion in three different human breast cancer cell lines, MDA-MB-231, MCF-7, and ZR-75-1.
Human NAT1 was knocked out using CRISPR/Cas9 technology and two different guide RNAs.
None of the NAT1 knockout (KO) cell lines exhibited detectable NAT1 activity when measured using its selective substrate p-aminobenzoic acid (PABA).
Endogenous acetyl coenzyme A levels (cofactor for acetylation pathways) in NAT1 KO cell lines were significantly elevated in the MDA-MB-231 (p<0.001) and MCF-7 (p=0.0127) but not the ZR-75-1 (p>0.05).
Although the effects of NAT1 KO on cell-doubling time were inconsistent across the three breast cancer cell lines, the ability of the NAT1 KO cell lines to form anchorage-independent colonies in soft agar was dramatically and consistently reduced in each of the breast cancer cell lines.
The NAT1 KO clones for MDA-MB-231, MCF-7, and ZR-75-1 had a reduction greater than 20-, 6-, and 7- folds in anchorage-independent cell growth, respectively, compared to their parental cell lines (p<0.0001, p<0.0001, and p<0.05, respectively).
The results indicate that NAT1 may be an important regulator of cellular acetyl coenzyme A levels and strongly suggest that elevated NAT1 expression in breast cancers contribute to their anchorage-independent growth properties and ultimately metastatic potential.
American Psychological Association (APA)
Stepp, Marcus W.& Salazar-González, Raúl A.& Hong, Kyung U.& Doll, Mark A.& Hein, David W.. 2019. N-Acetyltransferase 1 Knockout Elevates Acetyl Coenzyme A Levels and Reduces Anchorage-Independent Growth in Human Breast Cancer Cell Lines. Journal of Oncology،Vol. 2019, no. 2019, pp.1-11.
https://search.emarefa.net/detail/BIM-1184162
Modern Language Association (MLA)
Stepp, Marcus W.…[et al.]. N-Acetyltransferase 1 Knockout Elevates Acetyl Coenzyme A Levels and Reduces Anchorage-Independent Growth in Human Breast Cancer Cell Lines. Journal of Oncology No. 2019 (2019), pp.1-11.
https://search.emarefa.net/detail/BIM-1184162
American Medical Association (AMA)
Stepp, Marcus W.& Salazar-González, Raúl A.& Hong, Kyung U.& Doll, Mark A.& Hein, David W.. N-Acetyltransferase 1 Knockout Elevates Acetyl Coenzyme A Levels and Reduces Anchorage-Independent Growth in Human Breast Cancer Cell Lines. Journal of Oncology. 2019. Vol. 2019, no. 2019, pp.1-11.
https://search.emarefa.net/detail/BIM-1184162
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1184162