MOLECULAR CHARACTERIZATION OF DIFFERENTIAL GENE EXPRESSION PATTERNS ASSOCIATED WITH TAXOL RESISTANCE IN BREAST CANCER CELL LINES
Abstract
Breast cancer is still a significant health problem worldwide, especially triple-negative breast cancer (TNBC) which is a highly aggressive and poorly understood form of the disease with a tendency to become resistant to chemotherapy. Chemotherapy based on Taxol (paclitaxel) is well established in the treatment of breast cancer and resistance to this drug leads to poor therapeutic efficacy and recurrence and progression of the cancer. This study was designed to molecularly profile differential gene expression patterns in Taxol resistant breast cancer cell lines by using computational and bioinformatics approaches. Data on gene expression levels was analysed on a publicly available gene expression dataset including Taxol-resistant cell lines of breast cancer, namely BAS, MCF7, MDA and HS578T, that were analysed using Microsoft Excel. Genes with significant statistical differences (p-value < 0.05 and |logFC| > 1) were used to identify differentially expressed genes. The significant genes were divided into up and down regulated and then molecularly interpreted. The analysis revealed many transcriptional changes that are linked to Taxol resistance. SERPINB2, INHBA, PDPN and TP63 were significantly up regulated in several genes that are part of pathways involved in cell proliferation,
inflammatory signalling, migration and survival pathways. Conversely, genes linked to apoptosis regulation, metabolic balance and cellular adhesion (including IGFBP7, CLDN1, TFPI, and PPARGC1A) were significantly down regulated. The molecular expression patterns observed were complex and related to chemotherapy resistance. The study found that Taxol resistance in breast cancer cells is dependent upon the coordinated dysregulations of multiple molecular pathways. The genes identified could be used as markers and as targets for more effective chemotherapy in resistant breast cancer,and for the development of individual therapy plans.
Downloads
References
Bianchini, G., De Angelis, C., Licata, L., & Gianni, L. (2022). Treatment landscape of triple-negative breast cancer—
expanded options, evolving needs. Nature reviews Clinical oncology, 19(2), 91-113.
Chen, J., Zhu, M., Zou, L., Xia, J., Huang, J., Deng, Q., & Xu, R. (2020). Long non-coding RNA LINC-PINT
attenuates paclitaxel resistance in triple-negative breast cancer cells via targeting the RNA-binding protein
NONO. Acta Biochimica et Biophysica Sinica, 52(8), 801-809.
Chou, C. W., Huang, Y. M., Chang, Y. J., Huang, C. Y., & Hung, C. S. (2021). Identified the novel resistant biomarkers
for taxane-based therapy for triple-negative breast cancer. International journal of medical sciences, 18(12), 2521.
Cuthrell, K. M., & Tzenios, N. (2023). Breast cancer: updated and deep insights. International Research Journal of
Oncology, 6(1), 104-118.
Du, T., Shi, Y., Xu, S., Wan, X., Sun, H., & Liu, B. (2020). Long non-coding RNAs in drug resistance of breast
cancer. OncoTargets and therapy, 7075-7087.
Du, Y., Han, Y., Wang, X., Wang, H., Qu, Y., Guo, K., ... & Fu, L. (2022). Identification of Immune-Related breast
cancer chemotherapy resistance genes via bioinformatics approaches. Frontiers in Oncology, 12, 772723.
Gasca, J., Flores, M. L., Jiménez-Guerrero, R., Sáez, M. E., Barragán, I., Ruíz-Borrego, M., ... & Japón, M. A. (2020).
EDIL3 promotes epithelial–mesenchymal transition and paclitaxel resistance through its interaction with integrin
αVβ3 in cancer cells. Cell death discovery, 6(1), 86.
Goutsouliak, K., Veeraraghavan, J., Sethunath, V., De Angelis, C., Osborne, C. K., Rimawi, M. F., & Schiff, R. (2020).
Towards personalized treatment for early stage HER2-positive breast cancer. Nature Reviews Clinical
Oncology, 17(4), 233-250.
Hanker, A. B., Sudhan, D. R., & Arteaga, C. L. (2020). Overcoming endocrine resistance in breast cancer. Cancer
cell, 37(4), 496-513.
Jurj, A., Pop, L. A., Zanoaga, O., Ciocan-Cârtiţă, C. A., Cojocneanu, R., Moldovan, C., ... & Braicu, C. (2020). New
insights in gene expression alteration as effect of paclitaxel drug resistance in triple negative breast cancer cells. Cell
Physiol Biochem, 54(4), 648-664.
Li, A., Keck, J. M., Parmar, S., Patterson, J., Labrie, M., Creason, A. L., ... & Mitri, Z. I. (2021). Characterizing
advanced breast cancer heterogeneity and treatment resistance through serial biopsies and comprehensive
analytics. NPJ precision oncology, 5(1), 28. Schmid, P., Cortes, J., Pusztai, L., McArthur, H., Kümmel, S., Bergh,
J., & others. (2020). Pembrolizumab for early triple-negative breast cancer. The New England Journal of Medicine,
(9), 810–821.
Li, Y., Zhang, H., Merkher, Y., Chen, L., Liu, N., Leonov, S., & Chen, Y. (2022). Recent advances in therapeutic
strategies for triple-negative breast cancer. Journal of hematology & oncology, 15(1), 121.
Lian, B., Pei, Y. C., Jiang, Y. Z., Xue, M. Z., Li, D. Q., Li, X. G., ... & Shao, Z. M. (2020). Truncated HDAC9 identified
by integrated genome-wide screen as the key modulator for paclitaxel resistance in triple-negative breast
cancer. Theranostics, 10(24), 11092.
Liao, L., Zhang, Y. L., Deng, L., Chen, C., Ma, X. Y., Andriani, L., ... & Li, D. Q. (2023). Protein phosphatase 1
subunit PPP1R14B stabilizes STMN1 to promote progression and paclitaxel resistance in triple-negative breast
cancer. Cancer research, 83(3), 471-484.
Loizides, S., & Constantinidou, A. (2023). Triple negative breast cancer: Immunogenicity, tumor microenvironment,
and immunotherapy. Frontiers in genetics, 13, 1095839.
Madiseh, A. A. (2021). Taxol drug resistance cell lines in breast cancer [Dataset]. Kaggle.
https://www.kaggle.com/datasets/aliabedimadiseh/taxol-drug-resistance-cell-lines-in-breast-cancer
Qiu, Y., Lu, G., & Wu, Y. (2020). Upregulated CDKN2A expression may be an independent protective factor in
luminal-like breast cancer. Preprint at: https://assets. researchsquare. com/files/rs-29971/v1/6c4ff6f3-15de-49a6-909fe4ddb3a3a444. pdf.
Rakha, E. A., & Pareja, F. G. (2021, July). New advances in molecular breast cancer pathology. In Seminars in cancer
biology (Vol. 72, pp. 102-113). Academic Press.
Singh, D. D., & Yadav, D. K. (2021). TNBC: potential targeting of multiple receptors for a therapeutic breakthrough,
nanomedicine, and immunotherapy. Biomedicines, 9(8), 876.
Singh, D., Assaraf, Y. G., & Gacche, R. N. (2022). Long non-coding RNA mediated drug resistance in breast
cancer. Drug Resistance Updates, 63, 100851.
Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2021). Global cancer
statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a
cancer journal for clinicians, 71(3), 209-249.
Vagia, E., Mahalingam, D., & Cristofanilli, M. (2020). The landscape of targeted therapies in TNBC. Cancers, 12(4),
Won, K. A., & Spruck, C. (2020). Triple-negative breast cancer therapy: Current and future perspectives. International
journal of oncology, 57(6), 1245-1261.
Wu, T., Zhu, D., Wu, X., Zhang, N., & Zhang, Q. (2023). Taxol-resistant breast cancer cell-derived exosome-delivered
miR-187-5p regulates the growth of breast cancer cells via ABCD2 and Wnt/β-catenin signaling. Oncology
Letters, 25(3), 119.
Xia, Y. W., & Wang, S. B. (2021). Long noncoding RNA PVT1 facilitates high glucose‐induced cardiomyocyte death
through the miR‐23a‐3p/CASP10 axis. Cell Biology International, 45(1), 154-163.
Yan, G., Dai, M., Poulet, S., Wang, N., Boudreault, J., Daliah, G., ... & Lebrun, J. J. (2023). Combined in vitro/in vivo
genome-wide CRISPR screens in triple negative breast cancer identify cancer stemness regulators in paclitaxel
resistance. Oncogenesis, 12(1), 51.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 International Journal For Research In Biology & Pharmacy
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
In consideration of the journal, Green Publication taking action in reviewing and editing our manuscript, the authors undersigned hereby transfer, assign, or otherwise convey all copyright ownership to the Editorial Office of the Green Publication in the event that such work is published in the journal. Such conveyance covers any product that may derive from the published journal, whether print or electronic. Green Publication shall have the right to register copyright to the Article in its name as claimant, whether separately
or as part of the journal issue or other medium in which the Article is included.
By signing this Agreement, the author(s), and in the case of a Work Made For Hire, the employer, jointly and severally represent and warrant that the Article is original with the author(s) and does not infringe any copyright or violate any other right of any third parties, and that the Article has not been published elsewhere, and is not being considered for publication elsewhere in any form, except as provided herein. Each author’s signature should appear below. The signing author(s) (and, in
