ArticleOncogene2001
Expression of a truncated 100 kDa HER2 splice variant acts as an endogenous inhibitor of tumour cell proliferation.
Article in Oncogene, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 55 citations in OpenAlex.
- Soluble isoforms of EGFR family in breast cancer: Advances and clinical relevance (Review).Oncology letters · 2026Review
- SON is an essential RNA splicing factor promoting ErbB2 and ErbB3 expression in breast cancer.British journal of cancer · 2024Article
- The role of alternative pre-mRNA splicing in cancer progression.Cancer cell international · 2023Review
- HER2-PI9 and HER2-I12: two novel and functionally active splice variants of the oncogene HER2 in breast cancer.Journal of cancer research and clinical oncology · 2021Article
- Profiles of alternative splicing landscape in breast cancer and their clinical significance: an integrative analysis based on large-sequencing data.Annals of translational medicine · 2021Article
- HER2 splice variants in breast cancer: investigating their impact on diagnosis and treatment outcomes.Oncotarget · 2020Review
- Emerging Roles of SRSF3 as a Therapeutic Target for Cancer.Frontiers in oncology · 2020Review
- Genome-wide analysis of alternative transcripts in human breast cancer.Breast cancer research and treatment · 2015Article
- Article
- The HER2 Signaling Network in Breast Cancer--Like a Spider in its Web.Journal of mammary gland biology and neoplasia · 2014Review
- Interference-Free HER2 ECD as a Serum Biomarker in Breast Cancer.Journal of molecular biomarkers & diagnosis · 2014Article
- Alternative splicing generates a diacylglycerol kinase α transcript that acts as a dominant-negative modulator of superoxide production in localized aggressive periodontitis.Journal of periodontology · 2014Article
- TIMP-1 overexpression does not affect sensitivity to HER2-targeting drugs in the HER2-gene-amplified SK-BR-3 human breast cancer cell line.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2013Article
- Clinical Significance of HER-2 Splice Variants in Breast Cancer Progression and Drug Resistance.International journal of cell biology · 2013Article
- Modification of HER2 pre-mRNA alternative splicing and its effects on breast cancer cells.International journal of cancer · 2009Article
- A splice variant of HER2 corresponding to Herstatin is expressed in the noncancerous breast and in breast carcinomas.Neoplasia (New York, N.Y.) · 2008Article
- Genome-wide review of transcriptional complexity in mouse protein kinases and phosphatases.Genome biology · 2006Article
- Zinc finger transcription factors designed for bispecific coregulation of ErbB2 and ErbB3 receptors: insights into ErbB receptor biology.Molecular and cellular biology · 2005Article
- DNA-based therapeutics and DNA delivery systems: a comprehensive review.The AAPS journal · 2005Review
- RNAi-mediated gene-targeting through systemic application of polyethylenimine (PEI)-complexed siRNA in vivo.Gene therapy · 2005Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Overexpression of the HER2 (neu/c-erbB-2) oncogene frequently coincides with an aggressive clinical course of certain human adenocarcinomas. Expression and secretion of aberrant HER2 splice variants has been reported in various cell lines and tissues and can interfere with the oncogenic HER2 activity. Here we demonstrate, using two different approaches, that expression of a truncated 100 kDa HER2 variant which encodes the extracellular domain of HER2 (HER-ECD) inhibits growth factor-mediated tumour cell proliferation. A HER2-ECD cDNA encoding the truncated variant was overexpressed in MCF7 breast cancer cells. HER2-ECD overexpression decreased spontaneous proliferation of MCF7 cells as well as heregulin-mediated soft agar colony formation. Concomitantly, heregulin-induced phosphorylation of HER4 as well as downstream activation of p44/p42 MAP-kinases was decreased. To confirm these data, ribozymes were targeted to the 3'-untranslated region of the 2.3 kb HER2-ECD mRNA which is spontaneously expressed in MKN7 gastric cancer cells. HER2-ECD-targeted ribozymes downregulated HER2-ECD expression and enhanced EGF-mediated soft agar colony formation of MKN7 cells. In parallel, EGF-induced activation of p44/p42 MAP-kinases and activation of c-Fos expression were increased in ribozyme-transfected MKN7 cells. Finally, in RT-PCR we found a trend towards a progressive loss of 2.3 kb HER2-ECD mRNA expression in more advanced gastric tumours. These data show that the HER2-ECD variant inhibits growth factor-mediated tumour cell proliferation suggesting an important role during the progression of human cancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.