%0 Journal Article
%T Clinical Significance of HER-2 Splice Variants in Breast Cancer Progression and Drug Resistance
%A Claire Jackson
%A David Browell
%A Hannah Gautrey
%A Alison Tyson-Capper
%J International Journal of Cell Biology
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/973584
%X Overexpression of human epidermal growth factor receptor (HER-2) occurs in 20¨C30% 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 16HER-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. ˇ°Individualisedˇ± 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. 1. Introduction 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]. Figure 1: 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). In recent decades, there has been a paradigm shift from increasingly extensive and invasive surgery to ˇ°cureˇ± and prevent relapse to conservation surgery with lower morbidity and the use of adjuvant therapy to eliminate
%U http://www.hindawi.com/journals/ijcb/2013/973584/