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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

Histological images of breast carcinoma. Images of (a) ductal carcinoma no special type (NST), (b) ductal carcinoma in situ (DCIS), and (c) lobular carcinoma. (d) HercepTest positive staining: immunocytochemical staining indicates HER-2 overexpression in invasive breast cancer (Images courtesy of Dr. D. Hemming, Queen Elizabeth Hospital, Gateshead).
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fig1: Histological images of breast carcinoma. Images of (a) ductal carcinoma no special type (NST), (b) ductal carcinoma in situ (DCIS), and (c) lobular carcinoma. (d) HercepTest positive staining: immunocytochemical staining indicates HER-2 overexpression in invasive breast cancer (Images courtesy of Dr. D. Hemming, Queen Elizabeth Hospital, Gateshead).

Mentions: Breast cancer is a heterogeneous disease comprising subtypes of varied morphology, prognostic profiles, and clinical outcomes [1, 2]. Tumours arise from malignant transformation of hyperplasic epithelia within the breast [3], and numerous mutagenic changes contribute to the transformation process which abnormally alters the cellular environment. Atypical hyperplasic cells may progress to carcinoma in situ, categorised as ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS) [3] (Figure 1). These terms denote malignant cells restricted to ducts or acini of lobules. Carcinoma becomes invasive when atypical cells penetrate the basement membrane and spread into the surrounding stroma [3] (Figure 1). Cancer cells then have the potential to spread to surrounding skin or muscles or to metastasise to axillary lymph nodes or distant sites such as bone, liver, and brain where new tumours may form [3].


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)

Histological images of breast carcinoma. Images of (a) ductal carcinoma no special type (NST), (b) ductal carcinoma in situ (DCIS), and (c) lobular carcinoma. (d) HercepTest positive staining: immunocytochemical staining indicates HER-2 overexpression in invasive breast cancer (Images courtesy of Dr. D. Hemming, Queen Elizabeth Hospital, Gateshead).
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3713377&req=5

fig1: Histological images of breast carcinoma. Images of (a) ductal carcinoma no special type (NST), (b) ductal carcinoma in situ (DCIS), and (c) lobular carcinoma. (d) HercepTest positive staining: immunocytochemical staining indicates HER-2 overexpression in invasive breast cancer (Images courtesy of Dr. D. Hemming, Queen Elizabeth Hospital, Gateshead).
Mentions: Breast cancer is a heterogeneous disease comprising subtypes of varied morphology, prognostic profiles, and clinical outcomes [1, 2]. Tumours arise from malignant transformation of hyperplasic epithelia within the breast [3], and numerous mutagenic changes contribute to the transformation process which abnormally alters the cellular environment. Atypical hyperplasic cells may progress to carcinoma in situ, categorised as ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS) [3] (Figure 1). These terms denote malignant cells restricted to ducts or acini of lobules. Carcinoma becomes invasive when atypical cells penetrate the basement membrane and spread into the surrounding stroma [3] (Figure 1). Cancer cells then have the potential to spread to surrounding skin or muscles or to metastasise to axillary lymph nodes or distant sites such as bone, liver, and brain where new tumours may form [3].

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