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Amin, Risul
Publications (2 of 2) Show all publications
Jufvas, Å., Sjödin, S., Lundqvist, K., Amin, R., Vener, A. V. & Strålfors, P. (2013). Global differences in specific histone H3 methylation are associated with overweight and type 2 diabetes.. Clinical Epigenetics, 5(1), Article ID 15.
Open this publication in new window or tab >>Global differences in specific histone H3 methylation are associated with overweight and type 2 diabetes.
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2013 (English)In: Clinical Epigenetics, E-ISSN 1868-7083, Vol. 5, no 1, article id 15Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Epidemiological evidence indicates yet unknown epigenetic mechanisms underlying a propensity for overweight and type 2 diabetes. We analyzed the extent of methylation at lysine 4 and lysine 9 of histone H3 in primary human adipocytes from 43 subjects using modification-specific antibodies.

RESULTS: The level of lysine 9 dimethylation was stable, while adipocytes from type 2 diabetic and non-diabetic overweight subjects exhibited about 40% lower levels of lysine 4 dimethylation compared with cells from normal-weight subjects. In contrast, trimethylation at lysine 4 was 40% higher in adipocytes from overweight diabetic subjects compared with normal-weight and overweight non-diabetic subjects. There was no association between level of modification and age of subjects.

CONCLUSIONS: The findings define genome-wide molecular modifications of histones in adipocytes that are directly associated with overweight and diabetes, and thus suggest a molecular basis for existing epidemiological evidence of epigenetic inheritance.

Place, publisher, year, edition, pages
BioMed Central, 2013
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:liu:diva-99450 (URN)10.1186/1868-7083-5-15 (DOI)000329455000001 ()24004477 (PubMedID)
Available from: 2013-10-18 Created: 2013-10-18 Last updated: 2017-12-06Bibliographically approved
Karlsson, E., Pérez-Tenorio, G., Amin, R., Bostner, J., Skoog, L., Fornander, T., . . . Stål, O. (2013). The mTOR effectors 4EBP1 and S6K2 are frequently coexpressed, and associated with a poor prognosis and endocrine resistance in breast cancer: a retrospective study including patients from the randomised Stockholm tamoxifen trials.. Breast Cancer Research, 15(5), R96
Open this publication in new window or tab >>The mTOR effectors 4EBP1 and S6K2 are frequently coexpressed, and associated with a poor prognosis and endocrine resistance in breast cancer: a retrospective study including patients from the randomised Stockholm tamoxifen trials.
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2013 (English)In: Breast Cancer Research, ISSN 1465-5411, E-ISSN 1465-542X, Vol. 15, no 5, p. R96-Article in journal (Refereed) Published
Abstract [en]

INTRODUCTION: mTOR and its downstream effectors the 4E-binding protein 1 (4EBP1) and the p70 ribosomal S6 kinases (S6K1 and S6K2) are frequently upregulated in breast cancer, and assumed to be driving forces in tumourigenesis, in close connection with oestrogen receptor (ER) networks. Here, we investigated these factors as clinical markers in five different cohorts of breast cancer patients.

METHODS: The prognostic significance of 4EBP1, S6K1 and S6K2 mRNA expression was assessed with real-time PCR in 93 tumours from the treatment randomised Stockholm trials, encompassing postmenopausal patients enrolled between 1976 and 1990. Three publicly available breast cancer cohorts were used to confirm the results. Furthermore, the predictive values of 4EBP1 and p4EBP1_S65 protein expression for both prognosis and endocrine treatment benefit were assessed by immunohistochemical analysis of 912 node-negative breast cancers from the Stockholm trials.

RESULTS: S6K2 and 4EBP1 mRNA expression levels showed significant correlation and were associated with a poor outcome in all cohorts investigated. 4EBP1 protein was confirmed as an independent prognostic factor, especially in progesterone receptor (PgR)-expressing cancers. 4EBP1 protein expression was also associated with a poor response to endocrine treatment in the ER/PgR positive group. Cross-talk to genomic as well as non-genomic ER/PgR signalling may be involved and the results further support a combination of ER and mTOR signalling targeted therapies.

CONCLUSION: This study suggests S6K2 and 4EBP1 as important factors for breast tumourigenesis, interplaying with hormone receptor signalling. We propose S6K2 and 4EBP1 as new potential clinical markers for prognosis and endocrine therapy response in breast cancer.

Place, publisher, year, edition, pages
BioMed Central, 2013
Keywords
mTOR; S6 kinase; 17q21-23; 11q13; Gene amplification; Tamoxifen response
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-104178 (URN)10.1186/bcr3557 (DOI)000329763800024 ()24131622 (PubMedID)
Available from: 2014-02-10 Created: 2014-02-10 Last updated: 2017-12-06Bibliographically approved
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