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

To study the expression pattern and the role of the AP-1 (activating protein-1) family of transcription factors in endometrial carcinogenesis.

We performed Western blot experiments with specific antibodies for 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 status, Ki-67 expression and the expression levels of eight cell cycle regulatory proteins (cyclin D1, cyclin E, cyclin B1, cdk2, cdk4, p16, p21, and Rb).

Of the seven AP-1 factors, three (c-fos, fra2, 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 correlated with low ER and PR immunoreactivity and high grading (G3). On the other hand, correlations with classic cell cycle inhibitors (Rb, p16, p21) have also been observed for all AP-1 factors except c-jun and junD.

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 negative prognostic factor and/or implicated in tumor progression in endometrial cancer.