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Silencing human epidermal growth factor receptor-3 radiosensitizes human luminal A breast cancer cells.

ABSTRACT: Endocrine therapy and radiotherapy are the main treatments for luminal A breast cancer. However, drug and radiotherapy resistance could occur during long-term treatment, leading to local recurrence and distant metastasis. Some studies have found that drug resistance might be related to human epidermal growth factor receptor-3 (HER3) overexpression. However, whether HER3 plays a role in radiotherapy resistance is unknown. The purpose of this study is to elucidate the effect of HER3 in radiotherapy and to assess whether HER3 could be a potential target for radiosensitivity. We used retroviruses to construct stable low expression of HER3 in MCF-7 and ZR75-1cells. The CCK-8 assay was used to observe proliferation. Colony-forming assay was used to detect radiosensitivity. Flow cytometry was used to observe the cell cycle and apoptosis. Immunofluorescence assay was used to detect the number of ?H2AX foci in the nucleus with or without ionizing radiation (IR). Western blot analysis was used to verify the change of relative proteins. Nude mice were used to observe tumor growth in vivo. In our study, silencing HER3 reduced cell proliferation and clone formation ability after IR, so silencing HER3 increased the sensitivity of luminal A breast cancer cells to radiotherapy. In terms of radiosensitivity mechanisms, it is suggested that the silencing of HER3 enhanced IR-induced DNA damage, reduced DNA repair, and increased apoptosis and G2 /M arrest. In addition, silencing HER3 combined with IR clearly inhibited the transplanted tumor growth in vivo. Therefore, we concluded that HER3 played a role in radiotherapy resistance. Silencing HER3 increased the radiosensitivity of luminal A breast cancer cells and HER3 could be a potential target for radiosensitivity.

SUBMITTER: He G

PROVIDER: S-EPMC6272105 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Silencing human epidermal growth factor receptor-3 radiosensitizes human luminal A breast cancer cells.

He Guofeng G Di Xiaoke X Yan Jingjing J Zhu Caiqiang C Sun Xinchen X Zhang Shu S

Cancer science 20181022 12

Endocrine therapy and radiotherapy are the main treatments for luminal A breast cancer. However, drug and radiotherapy resistance could occur during long-term treatment, leading to local recurrence and distant metastasis. Some studies have found that drug resistance might be related to human epidermal growth factor receptor-3 (HER3) overexpression. However, whether HER3 plays a role in radiotherapy resistance is unknown. The purpose of this study is to elucidate the effect of HER3 in radiotherap ...[more]

PMID: 30259607

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Project description:The median survival of patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) has more than doubled, since the discovery of HER2-targeted treatments: it rose from less than 2?years in 2001 (prior introduction of trastuzumab) to more than 4?years in 2017. The initial generation of HER2-targeted therapies included trastuzumab with taxanes in the first line, followed by the addition of lapatinib and by a switch to another cytotoxic agent after progression. Results of CLEOPATRA, EMILIA, and TH3RESA trials have changed this clinical practice. The current consensus includes horizontal dual blockade (trastuzumab?+?pertuzumab) with taxanes or vinorelbine in the first line, followed by trastuzumab-emtansine (T-DM1) in the second line, with addition of lapatinib in the later lines of treatment. However, the fast and simultaneous development of new drugs led to a relative shortage of clinical evidence to support this sequence. Triple-positive breast cancers (TPBC), which express both hormonal receptors and HER2, constitute nearly half of HER2-positive cases. For these tumors, the current consensus is to add endocrine therapy after completion of cytotoxic treatment. Again, this consensus is not fully evidence-based. In view of the recent progress in treatment of estrogen-receptor positive breast cancers, a series of trials is evaluating addition of CDK4/6 inhibitors, aromatase inhibitors or fulvestrant to HER2-targeted and cytotoxic chemotherapy in TPBC patients. Despite the remarkable progress in treatment of HER2-positive breast cancer, metastatic disease is still incurable in the majority of patients. A wide range of novel therapies are under development to prevent and overcome resistance to current HER2-targeted agents. This review discusses pivotal clinical trials that have shaped current clinical practices, the current consensus recommendations, and the new experimental treatments in metastatic HER2-positive breast cancer.

Dataset Information

Silencing human epidermal growth factor receptor-3 radiosensitizes human luminal A breast cancer cells.

Publications

Silencing human epidermal growth factor receptor-3 radiosensitizes human luminal A breast cancer cells.

Similar Datasets

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