E. Rieger et al., EXPRESSION OF THE HOMEOBOX GENE HOXC4 IN KERATINOCYTES OF NORMAL SKINAND EPITHELIAL SKIN TUMORS IS CORRELATED WITH DIFFERENTIATION, Journal of investigative dermatology, 103(3), 1994, pp. 341-346
Homeobox (HOX) genes share a highly conserved 183-bp sequence. The enc
oded proteins are capable of binding to specific DNA sequences and fun
ctioning as transcription factors. HOX genes play a critical role in t
he temporal and spatial differentiation of cells during embryogenesis.
In several adult tissues, HOX genes are expressed in a constant, tiss
ue-specific pattern, whereas in malignant tumors of these tissues an a
ltered expression pattern was found. We investigated the expression of
HOXC4 in adult normal skin by reverse-transcription polymerase chain
reaction and non-radioactive RNA in situ hybridization. Moreover, HOXC
4 expression was studied in various epidermal neoplasms (solar keratos
is, six specimens; Bowen's disease, four; squamous cell carcinoma, nin
e; basal cell carcinoma, three) by RNA in situ hybridization. HOXC4 wa
s found to be expressed in the suprabasal layers of the epidermis in n
ormal skin specimens and the adjacent non-lesional epidermis of all ot
her specimens. Atypical keratinocytes of solar keratoses and Bowen's d
isease as well as basaloid cells of basal cell carcinomas were negativ
e. In squamous cell carcinoma, well differentiated areas with keratini
zation showed HOXC4 expression, whereas poorly differentiated areas we
re negative. Immunostaining with an antibody against cytokeratin 10, a
marker of epidermal differentiation, was performed. A good correlatio
n between the distribution pattern of HOXC4 and cytokeratin 10 in the
lesions examined was found. These results suggest that HOXC4 is expres
sed mainly in differentiated keratinocytes. Lack of differentiation (a
s in neoplastic cells) is accompanied by downregulation of HOXC4 expre
ssion.