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

Abstract

SummaryAlthough the sebaceous gland (SG) plays an important role in skin function, the mechanisms regulating SG differentiation and carcinoma formation are poorly understood. We previously reported that c-MYC overexpression stimulates SG differentiation. We now demonstrate roles for the androgen receptor (AR) and p53. MYC-induced SG differentiation was reduced in mice lacking a functional AR. High levels of MYC triggered a p53-dependent DNA damage response, leading to 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 exhibited high p53 and low AR expression. Thus, the consequences of overactivating MYC in the SG depend on whether AR or p53 is activated, as they form a regulatory axis controlling proliferation and differentiation.

BLIMP1 Is Required for Postnatal Epidermal Homeostasis but Does Not Define a Sebaceous Gland Progenitor under Steady-State Conditions

“…BLIMP1 + cells were found in the center of the meibomian glands, where the most highly differentiated sebocytes reside; they expressed FAS (Figures S1E and S1F), as reported previously (Cottle et al., 2013). Cells expressing BLIMP1 in preputial glands were also FAS + , confirming that they are indeed lipid-producing, differentiated sebocytes (Figures S1G and S1H).…”

Markers of Epidermal Stem Cell Subpopulations in Adult Mammalian Skin

“…However, in agreement with some work on BLIMP1 expression in mouse SGs (Magnú sdó ttir et al 2007;Lo Celso et al 2008;Cottle et al 2013), Sellheyer and Krahl (2010) identified BLIMP1 as a marker of terminally differentiated sebocytes, not as a sebocyte progenitor marker.…”

“…Also, mice with epidermal-specific deletion of Prdm1 displayed postnatal SG hyperplasia, suggesting a role for BLIMP1 in controlling the transition of quiescent stem cells to proliferative progenitor cells (Horsley et al 2006). However, this study is controversial because BLIMP1 is expressed in terminally differentiated cells of all epidermal compartments, including the SG (Magnú sdó ttir et al 2007;Lo Celso et al 2008;Cottle et al 2013;Page et al 2013).…”

Tumors of the eyelid - a histopathological study at tertiary care hospitals in Dhaka, Bangladesh

“…The etiology of sebaceous carcinoma is not entirely known. Human papilloma virus and increased expression of TP53 gene has been implicated as genetic factor in invasive sebaceous gland carcinoma [17,18]. In the present study, sebaceous gland carcinoma was found in 27.3% cases with malignant tumors.…”