An Alternative HER-2/neu Transcript of 8 kb Has an Extended 3′UTR and Displays Increased Stability in SKOV-3 Ovarian Carcinoma Cells

Doherty, Joni K.; Bond, Chris T.; Hua, Wenhui; Adelman, John P.; Clinton, Gail M.

doi:10.1006/gyno.1999.5467

Cited by 13 publications

(4 citation statements)

References 27 publications

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“…On the contrary, in OVCAR-3 cells, which do not overexpress ERBB2, we observed a progressive increase in transcriptional activity with longer promoter fragments. This result could be explained by the presence of a 8 kb transcript with an extended half-life in SK-OV-3 cells (Doherty et al, 1999a). Abnormal amounts of the erbB-2 mRNA could accumulate not only because of transcriptional upregulation, but also because of its stabilisation.…”

Section: Discussionmentioning

confidence: 99%

Different mechanisms are implicated in ERBB2 gene overexpression in breast and in other cancers

Vernimmen¹,

Guéders²,

Pisvin

et al. 2003

Br J Cancer

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The ERBB2 gene is overexpressed in 30% of breast cancers and this has been correlated with poor prognosis. ERBB2 is upregulated in other cancers such as prostate, pancreas, colon and ovary. In breast cancer cells, the mechanisms leading to ERBB2 gene overexpression are increased transcription and gene amplification. In these cancers, AP-2 transcription factors are involved in ERBB2 overexpression, and AP-2 levels are correlated with p185 c-erbB-2 levels. In this work, we wanted to know if the same molecular mechanisms are responsible for the ERBB2 upregulation in non-breast cancers. We compared ERBB2 gene copy number, p185 c-erbB-2 and mRNA levels with AP-2 levels in several ovary, prostate, colon and pancreas cancer cells. A moderate expression of erbB-2 mRNA and protein were observed in some cells without gene amplification. In contrast to breast cancer cells, AP-2 factors were absent or low in some non-breast cells which did express ERBB2. It is thus likely that AP-2 is not a major player in the increased levels of erbB-2 transcripts in non-breast cancer cells. The transcriptional activity of the ERBB2 promoter in colon and ovary cancer cells was estimated using reporter vectors. The results showed that the promoter regions involved in ERBB2 gene overexpression in breast cancer cells are different from those that lead to the gene upregulation in colon and ovary cancers. In conclusion, our results indicate that different transcriptional and post-transcriptional mechanisms are responsible for the increased levels of erbB-2 transcript and protein in breast and non-breast cancer cells.

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Section: Discussionmentioning

confidence: 99%

Different mechanisms are implicated in ERBB2 gene overexpression in breast and in other cancers

Vernimmen¹,

Guéders²,

Pisvin

et al. 2003

Br J Cancer

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“…Thereafter, the tPA signal/pro region was amplified using the primers 5Ј-ATTAGAATTCCACCA-TGGAT GCAATGAAGAGAGGG-3Ј containing an Eco RI site, and 5Ј-ATTATCTAGATCTGGCTCCTCTTCTGAATC-G-3Ј containing an Xba I site. The herstatin coding region with 6 histidine N-terminal tags (14,19) was amplified (excluding the signal sequence) using the primers 5Ј-AATTTCTAGAC-AAGTGTGCACCGGCACAGAC-3Ј containing an Xba I site and 5Ј-AAGGAAAAGCGGCCGCTCAGCCTTCATACCG-GGAC-3Ј containing a Not I site. The PCR-amplified products were purified, digested with restriction enzymes, and subcloned into the pcDNA3.1 expression plasmid (Invitrogen, San Diego, CA).…”

Section: Methodsmentioning

confidence: 99%

Antagonism of the human epidermal growth factor receptor family controls disease severity in murine collagen‐induced arthritis

Sumariwalla¹,

Pei²,

Zhang³

et al. 2008

Arthritis & Rheumatism

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Objective. To evaluate the therapeutic potential of the human epidermal growth factor receptor (HER) family inhibitor, herstatin, in an animal model of arthritis.Methods. Constructs of herstatin and modified tissue plasminogen activator (tPA)-herstatin were expressed in HEK 293T cells, and secreted protein was analyzed by Western blotting. Tissue PA-herstatin adenovirus (Ad-tPA-Her) was prepared, and titers established. Gene expression of Ad-tPA-Her was determined by polymerase chain reaction using HeLa cells. Pharmacokinetics of gene and protein expression in vivo in liver tissue and serum samples were confirmed via intravenous administration of Ad-tPA-Her. Clinical signs of disease were monitored in arthritic DBA/1 mice after therapeutic administration of Ad-tPA-Her, and histologic analysis of hind foot specimens was performed.Results. Native herstatin was not secreted in supernatants, while modified tPA-herstatin was detected in abundance. HeLa cells stably expressed the tPA-herstatin gene when infected with virus. Additionally, tPA-herstatin gene and protein expression was observed over time in mice treated with virus. Importantly, Ad-tPA-Her, when administered therapeutically to arthritic mice, controlled clinical and histologic signs of disease and reduced the number of joints with severe damage.Conclusion. Our results support the notion that the human epidermal growth factor receptor family has a role in the progression of collagen-induced arthritis. The novel tPA-herstatin fusion protein could be used as an effective therapeutic tool for control of inflammatory disorders involving an angiogenic component.

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“…Doherty et al, found that the 8-kb transcript had a half-life of 13 h compared to the 5.5 h for the 4.5-kb transcript. The increased stability of the longer transcript may confer a selective advantage for SKOV-3 cells by providing enhanced HER-2 expression [30]. C-myc is a protooncogene involved in the control of cellular proliferation, differentiation and apoptosis.…”

Section: Mutations In 3 Utr Cis-regulatory Elementsmentioning

confidence: 99%

Aberrant Regulation of Messenger RNA 3′‐Untranslated Region in Human Cancer

Silanes

Quesada

Esteller

2007

Analytical Cellular Pathology

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The messenger RNA 3′-untranslated region (3′UTR) is emerging as critically important in regulating gene expression at posttranscriptional levels. The 3′UTR governs gene expression via orchestrated interactions between mRNA structural components (cis-elements) and specific trans-acting factors (RNA-binding proteins and non-coding RNAs). Alterations in any of these components can lead to disease. Here, we review the mutations in 3′UTR regulatory sequences as well as the aberrant levels, subcellular localization, and posttranslational modifications of trans-acting factors that can promote or enhance the malignant phenotype of cancer cells. A thorough understanding of these alterations and their impact upon 3′UTR-directed posttranscriptional gene regulation will uncover promising new targets for therapeutic intervention.

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An Alternative HER-2/neu Transcript of 8 kb Has an Extended 3′UTR and Displays Increased Stability in SKOV-3 Ovarian Carcinoma Cells

Cited by 13 publications

References 27 publications

Different mechanisms are implicated in ERBB2 gene overexpression in breast and in other cancers

Different mechanisms are implicated in ERBB2 gene overexpression in breast and in other cancers

Antagonism of the human epidermal growth factor receptor family controls disease severity in murine collagen‐induced arthritis

Aberrant Regulation of Messenger RNA 3′‐Untranslated Region in Human Cancer

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