Altered expression of bcl-2 family member proteins in nonmelanoma skin cancer

BACKGROUND. Differentiation, proliferation, and cell death are coordinated tightly within the epidermis. Alterations within keratinocytes that disrupt these processes are believed to contribute to the development of nonmelano ma skin cancers (NMSC). In the current study the authors examined the expre ssion of selected members of the bcl-2 gene family in the skin and in case- matched samples of NMSC. METHODS. Immunohistochemistry was performed on tissue sections using antibo dies against bcl-2, bcl-x, bar, and bak. Case-matched frozen nonneoplastic skin samples and tumor tissues were used for Western blot analysis. RESULTS, In normal epidermis, bcl-2 oncoprotein is expressed in keratinocyt es of the basal layer but is down-regulated in suprabasal layers. The proap optotic bar protein is expressed at low levels in basal keratinocytes and i s up-regulated in suprabasal layers. The bcl-x and bak proteins both are ex pressed in the basal and spinous strata but are down-regulated in the granu lar cell layer. Both bcl-2 and bar were diffusely cytosolic whereas bcl-x a nd bak exhibited a distinct perinuclear distribution. Squamous cell carcino mas (SCC) were negative for bcl-2 whereas bcl-2 increased 5.5-fold in basal cell carcinomas (BCC). The distribution of bcl-x and bar proteins within B CC and SCC overlapped and were associated with squamous differentiation. Ba r protein was increased twofold to threefold in NMSC. An increase in bak pr otein also was observed in SCC. However, bak was diffusely cytosolic within BCC in contrast to the perinuclear distribution in nonneoplastic keratinoc ytes. CONCLUSIONS. These findings suggest that altered expression of bcl-2 family members may play a role in the pathogenesis of NMSC. (C) 1999 American Can cer Society.