Breast Cancer

NF-κB activation in human breast cancer specimens and its role in cell proliferation and apoptosis. Biswas, D.K. et al. Proc. Natl Acad. Sci. 101, 10137–10142 (2004)

Oestrogen-receptor-negative breast tumours represent a significant therapeutic hurdle because of a lack of effective molecular targets. Biswas et al. show that tumours that are oestrogen-receptor-negative but ERBB2-positive express increased levels of activated NF-κB. Suppression of NF-κB induced apoptosis in proliferating breast carcinoma cells, indicating that it might be a therapeutic target in these tumours.

Tumorigenesis

SMYD3 encodes a histone methyltransferase involved in the proliferation of cancer cells. Hamamoto, R. et al. Nature Cell Biol. 4 July 2004 (doi:10.1038/ncb1151)

Methylation of DNA and its associated histones is important for the activation and repression of transcription. Hamamoto et al. show that SMYD3 is overexpressed in most colorectal and liver tumours. A specific domain in SMYD3 was found to methylate histone H3 and — as part of a complex of proteins that includes RNA polymerase II — SMYD3 regulates the transcription of several important cell-cycle control genes. The deregulated expression of SMYD3 in these tumours might be a key factor in their development.

Therapeutics

Histone deacetylase inhibitors specifically kill nonproliferating tumour cells. Burgess, A. et al. Oncogene 5 July 2004 (doi:10.1038/sj.onc.1207893)

Burgess and colleagues showed that histone deacetylase inhibitors (HDIs) kill non-proliferating tumour cells, but not normal cells. The mechanism of cytotoxicity in non-proliferating cells involves the activation of the cyclin-dependent kinase inhibitor WAF1 — the same pathway that is activated by HDIs in proliferating cells — but non-proliferating cells take longer to activate the apoptosis machinery. Therefore, HDIs might be useful in the treatment of slowly proliferating tumours.

Gene Expression

Inhibition of fatty acid synthase (FAS) suppresses HER2/neu (erbB-2 ) oncogene overexpression in cancer cells. Menendez, J. A. et al. Proc. Natl Acad. Sci. USA 2 July 2004 (doi:10.1073/pnas.0403390101)

Levels of fatty-acid synthase (FAS) — an essential enzyme in the conversion of dietary carbohydrates to fatty acids — increase during breast cancer development, and hyperactivity of FAS is associated with aggressive disease. Javier Menendez et al. show that increased FAS activity in breast and ovarian cancer cell lines has an active role in malignant transformation by regulating key oncogenes, such as ERBB2.