Correlation of p27 protein expression with HER‐2/neu expression in breast cancer

Abstract

Strong expression of human epidermal growth factor receptor 2 (HER-2)/neu in breast cancer has been associated with poor prognosis. Reduced expression of p27(Kip1), a cyclin-dependent kinase inhibitor, correlates with poor clinical outcome in breast cancer. In this study, we provide a correlation between these two important prognostic markers in patients with breast cancer. Breast tumor screening using immunohistochemistry indicated that downregulation of p27 correlated with HER-2/neu overexpression in studying 11 normal breast tissues and 51 primary breast carcinomas. We found HER-2/neu protein overexpression in 20 (41%) of 49 breast cancers and low p27 protein expression in 47 (92%) of 51 breast cancers. All 20 (100%) of the tumors that overexpressed HER-2/neu had low levels of p27 protein product; this correlation was statistically significant (P = 0.035). Decreasing p27 expression correlated with increasing HER-2/neu activity. Our results suggest that one function of the HER-2/neu product is to downregulate p27 expression in breast cancer. This study may be significant in selecting patients for HER-2/neu antibody therapy in the future. Mol. Carcinog. 30:169--175, 2001.

HER2-targeting Antibodies Modulate the Cyclin-dependent Kinase Inhibitor p27Kip1 via Multiple Signaling Pathways

“…43 A study of 51 primary breast carcinomas showed that all the tumors that overexpressed HER2 had low levels of p27 Kip1 protein. 44 These studies strongly indicate that HER2 overexpression correlates tightly with decreasing p27 Kip1 expression.…”

The oncogene HER2: its signaling and transforming functions and its role in human cancer pathogenesis

“…Akt is activated in HER2-amplified breast cancers (reviewed above) and activated Akt phosphorylates p27 inhibiting its function by excluding it from the nucleus (Liang et al, 2002;Shin et al, 2002;Viglietto et al, 2002). Several clinical studies have also established that HER2-overexpressing breast cancers have reduced p27 expression compared with other types of breast cancers (Newman et al, 2001;Loden et al, 2003;Spataro et al, 2003). HER2 mediates p27 degradation likely through mechanisms that involve MAPK (Yang et al, 2000;Donovan et al, 2001;Lenferink et al, 2001).…”

Negative cell cycle regulator 14-3-3σ stabilizes p27 Kip1 by inhibiting the activity of PKB/Akt

“…The general immunohistochemical staining scheme was performed as described previously (Newman et al, 2001). Antibody detection was performed with the ABC substrate kit (Vector Laboratories, Burlingame, CA, USA), and slides were counterstained with hematoxylin.…”