Isoform-specific expression of T-type voltage-gated calcium channels and estrogen receptors in breast cancer reveals specific isoforms that may be potential targets

Sekar, Shwetha and Subbamanda, Yashashwini and Pullaguri, Narasimha and Sharma, Ankush and Sahu, Chittaranjan and Kumar, Rahul and Bhargava, Anamika (2022) Isoform-specific expression of T-type voltage-gated calcium channels and estrogen receptors in breast cancer reveals specific isoforms that may be potential targets. Current Research in Biotechnology, 4. pp. 459-467. ISSN 2590-2628

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Purpose: T-type voltage-gated calcium channels (TTCCs) have been implicated as novel targets in breast cancer treatment; however, the knowledge of isoform-specific expression of TTCCs in the pathology of breast cancer remains limited. Although estrogen receptor blockers are clinically beneficial, patients often show resistance to these compounds. Interestingly, TTCCs are modulated by estrogen in the brain and heterologous expression systems; however, whether TTCCs and estrogen receptors (ERs) interact in breast tissue is unknown. In addition, the isoform specific expression of TTCCs and ERs in breast cancer subtypes has not been determined. Methods: We investigated the alterations in TTCC and ER gene isoforms, their co-occurrence and the association of alterations with patient survival in breast cancer and its subtypes by using The Cancer Genome Atlas (TCGA) dataset. To understand the functional roles of TTCC and ESR genes in breast cancer, we studied cell proliferation in the presence of a TTCC inhibitor and ER activator. Results: Our results from the TCGA dataset indicated differential alterations in TTCC isoform expression in patients with breast cancer, including downregulation of CACNA1G and upregulation of CACNA1H, and CACNA1I. Among ER isoforms, upregulation of ESR1 and downregulation of ESR2 were observed. Survival analysis indicated that ESR2 may be a potential target, because its downregulation was associated with shorter overall survival. Subtype specific survival analysis revealed CACNA1G, CACNA1H and ESR2 as potential novel targets in luminal type breast cancer. Alterations in ESR2 co-occurred with alterations in CACNA1H and CACNA1I, thus warranting investigation of potential crosstalk. Experimental data indicated that targeting both TTCCs and ESR2 may be beneficial for luminal type breast cancer. Conclusion: Our data provide novel insights into the altered expression of TTCC and ESR gene isoforms in breast cancer subtypes and suggest novel therapeutic targets. © 2022 The Author(s)

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IITH Creators:
IITH CreatorsORCiD
Kumar, Rahul
Bhargava, Anamika
Item Type: Article
Additional Information: This work was supported by the Indian Institute of Technology Hyderabad (IITH) and ECR-, SERB-DST (ECR/2017/000242) grants to AB. Ministry of Education, India fellowship to SS, Department of Biotechnology, India fellowship to AS and CSIR, India research fellowship to YSD. The authors have no relevant financial or non-financial interests to disclose. This article does not contain any studies in human participants or animals performed by any of the authors. Not applicable. Not applicable. All data are available in cBioPortal and UALCAN, except qPCR and cell proliferation experiments.
Uncontrolled Keywords: Breast Cancer; Estrogen receptors; Isoforms; T-type calcium channels
Subjects: Others > Biotechnology
Divisions: Department of Biotechnology
Depositing User: . LibTrainee 2021
Date Deposited: 11 Oct 2022 04:05
Last Modified: 11 Oct 2022 04:05
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