Expression pattern of the AP-1 family in endometrial cancer: correlations with cell cycle regulators

Purpose: To study the expression pattern and the role of the AP-1 (activati ng protein-1) family of transcription factors in endometrial carcinogenesis . Methods: We performed Western blot experiments with specific antibodies f or each of the AP-1 proteins (c-jun, junB, junD, c-fos, fosB, fra-1, fra-2) with 41 endometrial carcinomas. Expression levels of the AP-1 factors were correlated with clinico-pathologic tumor parameters, steroid receptor stat us, Ki-67 expression and the expression levels of eight cell cycle regulato ry proteins (cyclin D1, cyclin E. cyclin B1, cdk2. cdk4, p16, p21. and Rb). Results: Of the seven AP-1 factors, three (c-fos, fra-2, and junB) clearly showed higher expression levels in tumors when compared to matched normal endometrial samples. These factors also correlated significantly with cell cycle promoters (c-fos with cyclin E, cyclin B1, cdk2, and cdk4; fra-2 with cyclin B1; and junB with cyclin D1). Furthermore, high c-fos expression co rrelated with low ER and PR immunoreactivity and high grading (G3). On the other hand, correlations with classic cell cycle inhibitors (Rb, p16 p21) h ave also been observed for all AP-1 factors except c-jun and junD. Conclusi ons: Our results indicate that the AP-1 family of transcription factors is probably implicated in the regulation of cell cycle progression and control in endometrial carcinomas. In particular, c-fos might be an additional neg ative prognostic factor and/or implicated in tumor progression in endometri al cancer.