P8 is critical for tumour development induced by rasV12 mutated protein and E1A oncogene

The p8 protein is involved in the cellular stress response of many tissues. Because p8 is overexpressed in many cancers, we investigated whether its expression was required for tumour development. Mouse embryo fibroblasts (MEFs) from p8(+/+) and p8(-/-) animals were transformed with the pBaberas(V12)/E1A retroviral vector, which expresses both the ras(V12) mutated protein and the E1A oncogene. As expected, transformed p8(+/+) MEFs could form colonies in soft agar. However, transformed p8(-/-) MEFs could not. In addition, subcutaneous or intraperitoneal injections of transformed p8(+/+) MEFs always led to tumour formation in nude mice, but, again, no tumour was observed with transformed p8(-/-) MEFs. However, restoring p8 expression in transformed p8(-/-) MEFs before injection led to tumour formation. In the tumours, p8 expression was induced during tumour development. It was concluded that p8 expression in transformed MEFs is necessary for tumour formation, suggesting that the stress-response mechanisms governed by p8 are required for tumour establishment.