Altered sirtuin expression is associated with node-positive breast cancer

Abstract

Sirtuins are genes implicated in cellular and organismal ageing. Consequently, they are speculated to be involved in diseases of ageing including cancer. Various cancers with widely differing prognosis have been shown to have differing and characteristic expression of these genes; however, the relationship between sirtuin expression and cancer progression is unclear. In order to correlate cancer progression and sirtuin expression, we have assessed sirtuin expression as a function of primary cell ageing and compared sirtuin expression in normal, 'nonmalignant' breast biopsies to breast cancer biopsies using real-time polymerase chain reaction (PCR). Levels of SIRT7 expression were significantly increased in breast cancer (P<0.0001). Increased levels of SIRT3 and SIRT7 transcription were also associated with node-positive breast cancer (P<0.05 and P<0.0001, respectively). This study has demonstrated differential sirtuin expression between nonmalignant and malignant breast tissue, with consequent diagnostic and therapeutic implications.

Figure 1

Sirtuin expression in serially passaged mammary epithelial cell cultures. The figure shows relative sirtuin gene expression in serially passaged cells relative to 18 s rRNA gene expression. Mean data are plotted ±s.d.

Figure 2

Senescence associated-β-galactosidase expression in serially passaged primary and immortalised mammary epithelial cells. Mean SA-β-Gal expression is shown ±s.d.

Figure 3

p16 and p21 expression in successively passaged breast cells. Histograms show the relative gene expression for p16 and p21 relative to 18 s rRNA expression in primary cell cultures and immortalized breast cell lines. Data is plotted as means±s.em.

Figure 4

SIRT7 expression in normal and breast cancer biopsies. HIstograms show relative sirtuin gene expression in nonmalignant and malignant breast biopsies, relative to an 18 s rRNA control. Data show mean sirtuin expression ±s.e.m.

Figure 5

SIRT7 expression in breast biopsies by nodal status. The histogram shows relative sirtuin gene expression in nonmalignant and lymph node-positive and -negative breast cancer biopsies. Data are plotted as mean sirtuin expression ±s.e.m.

Figure 6

SIRT3 expression in breast biopsies by nodal status. The histogram shows relative sirtuin gene expression in nonmalignant and lymph node-positive and -negative breast cancer biopsies. Data are plotted as mean sirtuin expression ±s.e.m.