Presence of exon 5-deleted oestrogen receptor in human breast cancer: Functional analysis and clinical significance
| Autor: | Sami Shousha, C. N. Rees, B. Dagg, R. C. Coope, J. J. Gomm, A. J. Desai, V. Thirunavukkarasu, Paul E. Pace, N. Groome, J. Walters, R. C. Coombes, Simak Ali, YA Luqmani |
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| Jazyk: | angličtina |
| Rok vydání: | 1997 |
| Předmět: |
Cancer Research
polymerase chain reaction BINDING DOMAINS Exon Mice Tumor Cells Cultured exon GLUCOCORTICOID RECEPTORS Sequence Deletion Aged 80 and over Mice Inbred BALB C biology DELETION VARIANT Antibodies Monoclonal Exons Middle Aged oestrogen receptor Gene Expression Regulation Neoplastic Receptors Estrogen COS Cells Immunohistochemistry Female Antibody transcription MESSENGER-RNA Receptors Progesterone Life Sciences & Biomedicine Research Article EXPRESSION Adult Breast Neoplasms Enzyme-Linked Immunosorbent Assay Transfection Breast cancer breast neoplasm Progesterone receptor medicine Animals Humans RNA Messenger Oncology & Carcinogenesis Aged DNA Primers Messenger RNA Science & Technology IDENTIFICATION Cancer medicine.disease ONCOLOGY Molecular biology GENE Survival Analysis Reverse transcriptase HUMAN ESTROGEN-RECEPTOR biology.protein TRANSCRIPTIONAL ACTIVATION 1112 Oncology And Carcinogenesis RESISTANCE |
| Zdroj: | British Journal of Cancer |
| Popis: | A variant form of the human oestrogen receptor (ER) mRNA lacking sequences encoded within exon 5 has been described (Fuqua SAW, Fitzgerald SD, Chamness GC, Tandon AK, McDonnell DP, Nawaz Z, O'Malloy BW, McGuire WL 1991, Cancer Res 51: 105-109). We have examined the expression of the exon 5-deleted ER (HE delta5) mRNA variant in breast biopsies using reverse transcriptase polymerase chain reaction (RT - PCR). HE delta5 mRNA was present in only 13% of non-malignant breast tissues compared with 32% of carcinomas (95% CI, P=0.05). Presence of the HE delta5 mRNA was associated with the presence of immunohistochemically detected ER (P=0.015) and progesterone receptor (PR) (P=0.02). There was a positive correlation between the presence of HE delta5 and disease-free survival (P=0.05), suggesting that the presence of HE delta5 may be an indicator of better prognosis. We have raised a monoclonal antibody specific to the C-terminal amino acids of HE delta5. This antibody recognized the variant but not the wild-type ER protein. We show that HE delta5 protein is present in breast cancer using immunohistochemical techniques. We also analysed trans-activation by HE delta5 in mammalian cells and showed that, in MCF-7 cells, HE delta5 competes with wild-type ER to inhibit ERE-dependent trans-activation. Our results indicate that this variant is unlikely to be responsible for endocrine resistance of breast cancer, but its presence at both the mRNA and protein level suggest that it may, nevertheless, be involved in regulating the expression of oestrogen-responsive genes in breast cancer. Images Figure 1 Figure 3 p1180-a Figure 4 |
| Databáze: | OpenAIRE |
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