C-MYC-Induced Sebaceous Gland Differentiation Is Controlled by an Androgen Receptor/p53 Axis

The study investigated the mechanisms behind sebaceous gland (SG) differentiation and carcinoma formation, focusing on the roles of the androgen receptor (AR) and p53. It was found that c-MYC overexpression stimulated SG differentiation, but this effect was reduced in mice lacking a functional AR. High levels of MYC induced a p53-dependent DNA damage response, leading to an accumulation of proliferative SG progenitors and inhibition of AR signaling. Conversely, testosterone treatment or p53 deletion activated AR signaling and restored MYC-induced differentiation. Poorly differentiated human sebaceous carcinomas showed high p53 and low AR expression, indicating that the balance between AR and p53 activation is crucial for controlling SG proliferation and differentiation.