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 nonmelanoma skin cancers (NMSC). In the current study the authors examined the expression 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 antibodies against bcl-2, bcl-x, bax, 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 keratinocytes of the basal layer but is down-regulated in suprabasal layers. The proapoptotic bax protein is expressed at low levels in basal keratinocytes and is up-regulated in suprabasal layers. The bcl-x and bak proteins both are expressed in the basal and spinous strata but are down-regulated in the granular cell layer. Both bcl-2 and bax were diffusely cytosolic whereas bcl-x and bak exhibited a distinct perinuclear distribution. Squamous cell carcinomas (SCC) were negative for bcl-2 whereas bcl-2 increased 5.5-fold in basal cell carcinomas (BCC). The distribution of bcl-x and bax proteins within BCC and SCC overlapped and were associated with squamous differentiation. Bax protein was increased twofold to threefold in NMSC. An increase in bak protein also was observed in SCC. However, bak was diffusely cytosolic within BCC in contrast to the perinuclear distribution in nonneoplastic keratinocytes.


CONCLUSIONS
These findings suggest that altered expression of bcl-2 family members may play a role in the pathogenesis of NMSC.
Delehedde
M
M
Department of Molecular Pathology, The University of Texas, M. D. Anderson Cancer Center, Houston 77030, USA.
Cho
S H
SH
Sarkiss
M
M
Brisbay
S
S
Davies
M
M
El-Naggar
A K
AK
McDonnell
T J
TJ
D017209:Apoptosis; D015153:Blotting, Western; D002280:Basal Cell Carcinoma / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D015536:Down-Regulation; D004817:Epidermis / Q000737:chemistry; D006801:Humans; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000737:chemistry; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000276:immunology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis* / Q000276:immunology; D012878:Skin Neoplasms / Q000235:genetics*; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
C494826:BAX protein, human; C494811:BCL2L1 protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein