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Clinical Significance of HER-2 Splice Variants in Breast Cancer Progression and Drug Resistance.

Jackson C, Browell D, Gautrey H, Tyson-Capper A - Int J Cell Biol (2013)

Bottom Line: Overexpression of human epidermal growth factor receptor (HER-2) occurs in 20-30% of breast cancers and confers survival and proliferative advantages on the tumour cells making HER-2 an ideal therapeutic target for drugs like Herceptin.Continued delineation of tumour biology has identified splice variants of HER-2, with contrasting roles in tumour cell biology.For example, the splice variant Δ16HER-2 (results from exon 16 skipping) increases transformation of cancer cells and is associated with treatment resistance; conversely, Herstatin (results from intron 8 retention) and p100 (results from intron 15 retention) inhibit tumour cell proliferation.

View Article: PubMed Central - PubMed

Affiliation: Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.

ABSTRACT
Overexpression of human epidermal growth factor receptor (HER-2) occurs in 20-30% of breast cancers and confers survival and proliferative advantages on the tumour cells making HER-2 an ideal therapeutic target for drugs like Herceptin. Continued delineation of tumour biology has identified splice variants of HER-2, with contrasting roles in tumour cell biology. For example, the splice variant Δ16HER-2 (results from exon 16 skipping) increases transformation of cancer cells and is associated with treatment resistance; conversely, Herstatin (results from intron 8 retention) and p100 (results from intron 15 retention) inhibit tumour cell proliferation. This review focuses on the potential clinical implications of the expression and coexistence of HER-2 splice variants in cancer cells in relation to breast cancer progression and drug resistance. "Individualised" strategies currently guide breast cancer management; in accordance, HER-2 splice variants may prove valuable as future prognostic and predictive factors, as well as potential therapeutic targets.

No MeSH data available.


Related in: MedlinePlus

Patterns of HER-2 in different cancers. Bar chart shows genetic changes in a wide range of different tumours and cancer types, including mutation, deletion, and amplification. Note that amplification is particularly prevalent in invasive carcinoma of the breast. Data was generated using the cBIO Cancer Genomics Portal [14, 15].
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fig3: Patterns of HER-2 in different cancers. Bar chart shows genetic changes in a wide range of different tumours and cancer types, including mutation, deletion, and amplification. Note that amplification is particularly prevalent in invasive carcinoma of the breast. Data was generated using the cBIO Cancer Genomics Portal [14, 15].

Mentions: HER-2 has been acknowledged as a protooncogene since a mutated form, the NEU oncogene, was isolated using cell transformation studies in the rat that used tumour DNA [13]. Moreover, amplification of the HER-2 gene occurs in a number of different cancers and is particularly prevalent in invasive carcinoma of the breast (Figure 3) [14–16]. HER-2 protein is overexpressed in many human cancers and associated with 20–30% of breast cancers [7, 17]. High levels of the receptor result in enhancement of oncogenic signalling pathways [12]. Consequently, HER-2-positive tumours are associated with increased metastatic potential, poor prognosis, and recurrence [18, 19].


Clinical Significance of HER-2 Splice Variants in Breast Cancer Progression and Drug Resistance.

Jackson C, Browell D, Gautrey H, Tyson-Capper A - Int J Cell Biol (2013)

Patterns of HER-2 in different cancers. Bar chart shows genetic changes in a wide range of different tumours and cancer types, including mutation, deletion, and amplification. Note that amplification is particularly prevalent in invasive carcinoma of the breast. Data was generated using the cBIO Cancer Genomics Portal [14, 15].
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3713377&req=5

fig3: Patterns of HER-2 in different cancers. Bar chart shows genetic changes in a wide range of different tumours and cancer types, including mutation, deletion, and amplification. Note that amplification is particularly prevalent in invasive carcinoma of the breast. Data was generated using the cBIO Cancer Genomics Portal [14, 15].
Mentions: HER-2 has been acknowledged as a protooncogene since a mutated form, the NEU oncogene, was isolated using cell transformation studies in the rat that used tumour DNA [13]. Moreover, amplification of the HER-2 gene occurs in a number of different cancers and is particularly prevalent in invasive carcinoma of the breast (Figure 3) [14–16]. HER-2 protein is overexpressed in many human cancers and associated with 20–30% of breast cancers [7, 17]. High levels of the receptor result in enhancement of oncogenic signalling pathways [12]. Consequently, HER-2-positive tumours are associated with increased metastatic potential, poor prognosis, and recurrence [18, 19].

Bottom Line: Overexpression of human epidermal growth factor receptor (HER-2) occurs in 20-30% of breast cancers and confers survival and proliferative advantages on the tumour cells making HER-2 an ideal therapeutic target for drugs like Herceptin.Continued delineation of tumour biology has identified splice variants of HER-2, with contrasting roles in tumour cell biology.For example, the splice variant Δ16HER-2 (results from exon 16 skipping) increases transformation of cancer cells and is associated with treatment resistance; conversely, Herstatin (results from intron 8 retention) and p100 (results from intron 15 retention) inhibit tumour cell proliferation.

View Article: PubMed Central - PubMed

Affiliation: Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.

ABSTRACT
Overexpression of human epidermal growth factor receptor (HER-2) occurs in 20-30% of breast cancers and confers survival and proliferative advantages on the tumour cells making HER-2 an ideal therapeutic target for drugs like Herceptin. Continued delineation of tumour biology has identified splice variants of HER-2, with contrasting roles in tumour cell biology. For example, the splice variant Δ16HER-2 (results from exon 16 skipping) increases transformation of cancer cells and is associated with treatment resistance; conversely, Herstatin (results from intron 8 retention) and p100 (results from intron 15 retention) inhibit tumour cell proliferation. This review focuses on the potential clinical implications of the expression and coexistence of HER-2 splice variants in cancer cells in relation to breast cancer progression and drug resistance. "Individualised" strategies currently guide breast cancer management; in accordance, HER-2 splice variants may prove valuable as future prognostic and predictive factors, as well as potential therapeutic targets.

No MeSH data available.


Related in: MedlinePlus