Dj. Fitzgerald et al., EXPRESSION AND FUNCTION OF CONNEXIN IN NORMAL AND TRANSFORMED HUMAN KERATINOCYTES IN CULTURE, Carcinogenesis, 15(9), 1994, pp. 1859-1865
We have studied the gap junctional intercellular communication (GJIC)
of immortalized and tumourigenic human keratinocyte cell lines and of
a spontaneously immortalized non-tumourigenic and a highly differentia
ting keratinocyte cell line (HaCaT) as the control. In homologous cult
ures, the GJIC capacity of five squamous cell carcinoma-derived cell l
ines was 1-27% that of the HaCaT cells. Ha-ras-transfected HaCaT cells
with tumourigenic potential and an SV40 DNA-immortalized cell line ha
d markedly reduced GJIC capacities, Northern analysis and immunohistoc
hemistry showed that connexin (Cx) 43 is the major gap junction protei
n expressed in the communicating cells. They do not express Cx 26 or 3
2. The low or absent communication observed in certain cell lines was
due in some to a lack of Cx 43 gene expression, but in others to aberr
ant localization of the gap junction protein. GJIC of these cell lines
, as well as that of primary normal human epidermal keratinocytes, was
susceptible to 12-O-tetra-decanoylphorbol-13-acetate-mediated inhibit
ion. Moreover, GJIC of HaCaT cells and their tumourigenic derivatives
is Ca2+-dependent. These results, when compared with those previously
obtained for mouse keratinocyte cell lines, reveal that GJIC of human
keratinocytes was correlated to the degree of differentiation and is c
ontrolled in a similar way to that of murine keratinocytes. Aberrant G
JIC seems to be a common feature of human and murine skin carcinogenes
is.