Cyclin E overexpression, a negative prognostic factor in breast cancer with strong correlation to oestrogen receptor status

Abstract

Summary Cyclin E is a GI cyclin which has been proposed to be one of the key regulators of the important GI/S transition, and could consequently be a potential deregulated molecule in tumours. Recently, it has been observed that cyclin E is overexpressed in a variety of malignancies including breast cancer and that several isoforms of the protein exists. In this study we have characterised the cyclin E expression in 114 tumour specimens from patients with primary breast cancer using Western blotting. Various expression of cyclin E was observed among tumours and a group of 27 patients out of 100 patients with stage I-III disease, identified as having tumours with high cycin E levels, had a significantly increased risk of death and relapse from breast cancer (P=0.0002 and P=0.015 respectively). Even in the subgroup of axillary node-negative patients the cyclin E level was of prognostic importance. There was also a strong association between cyclin E expression and oestrogen receptor status (P<0.00001), and tumours with high cyclin E expression were in general oestrogen receptor negative, suggesting a potential role for cyclin E in mechanisms responsible for oestrogenindependent tumour growth.

Cell cycle basis for the onset and progression of c-Myc-induced, TGFα-enhanced mouse mammary gland carcinogenesis

“…The overexpression of cyclin E may result from a synergy between TGFa and cMyc, because expression of cyclin E is not pronounced in the hyperplastic epithelium from either tgfa or c-myc animals. This hypothesis is consistent with the observation in human breast cancer, that overexpression of cyclin E is correlated with increased tumor grade (Nielsen et al, 1996;Keyomarsi, et al, 1994). Moreover, a well-known, but mechanistically-unclear phenomenon is that overexpression of the c-myc gene alone is insu cient for transformation of most types of cells either in vitro or in vivo; cooperation of c-myc with growth factors (like TGFa) or some oncogenes (such as .…”

Lack of cyclin E immunoreactivity in non-malignant breast and association with proliferation in breast cancer

“…The frequency of cyclin E expression may be underestimated in studies utilizing Western blotting techniques, because of the heterogeneity and presence of non-cancerous cells in the sample and varied amounts of extracellular stromal proteins. However, the percentage of carcinomas considered to have greater reactivity was very similar to that found by Nielsen et al (1996).…”

“…Overexpression of cyclin E has been observed in 10 out of 10 breast cancer cell lines and breast tissue using Western blotting techniques (Keyomarsi and Pardee, 1993;Keyomarsi et al, 1994;Nielsen et al, 1996). It has been suggested that deregulation of cyclin E may be a factor contributing to the malignant phenotype (Keyomarsi and Pardee, 1993;Keyomarsi et al, 1994;Dutta et al, 1995).…”

“…It has been suggested that deregulation of cyclin E may be a factor contributing to the malignant phenotype (Keyomarsi and Pardee, 1993;Keyomarsi et al, 1994;Dutta et al, 1995). Recently, Western blotting of 114 breast tumour specimens showed that women with tumours with high cyclin E levels had a significantly increased risk of death and relapse from breast cancer (Nielsen et al, 1996). Keyomarsi et al (1994) also showed that the alterations in cyclin E expression became greater with increasing grade and stage (Keyomarsi et al, 1994).…”

“…In the search for newer markers which can provide information about breast cancer behaviour, attention has recently focused on the role of cyclin E. Previous studies have demonstrated that Received 22 January 1997Revised 29April 1997 Accepted 12 May 1997 Correspondence to: RA Walker overexpression correlates with tumour aggressiveness (Keyomarsi et al, 1994;Nielsen et al, 1996). These studies investigated expression using Western blotting.…”