Changes in gap junctional intercellular communication in mouse skin carcinogenesis.
Gap junction intercellular communication (GJIC) has been measured in cell lines that represent different stages of chemically induced mouse skin carcinogenesis. No significant difference in GJIC, as measured by dye spread, was found in cultures of normal keratinocyte, papilloma or squamous carcinoma cell lines. There was no correlation, in this system, between the presence of a mutant Ha-ras gene and down-regulation of communication. There was, however, a marked decrease in GJIC (80-90%) on progression from squamous to spindle carcinoma cells. Measurement of GJIC in somatic cell hybrids shows that the genetic defect responsible for this down-regulation is recessive and is common to two independently isolated spindle cell lines. No abnormalities were found in the spindle cells in expression of connexin 43, a cell component involved in gap junction formation and permeability. However, expression of E-cadherin, a cell-cell adhesion molecule implicated in the process of gap junction formation, was missing in the spindle carcinoma cells. Introduction of an E-cadherin cDNA into the spindle cells partially restored junctional communication without causing any noticeable alterations in cell morphology. During the study a non-tumourigenic keratinocyte line, a sub-clone of a normal keratinocyte line, was also found to have a low level of GJIC. However, the defect in this line was shown, by genetic complementation in somatic cell hybrids, to be different from that in the spindle carcinoma cell lines. Consistent with these data, analysis by immunofluorescence shows an abnormal distribution of connexin 43 in these cells.
Holden
P R
PR
The Beatson Institute for Cancer Research, CRC Beatson Laboratories, Bearsden, Glasgow, UK.
McGuire
B
B
Stoler
A
A
Balmain
A
A
Pitts
J D
JD
D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002277:Carcinoma / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D002450:Cell Communication / Q000235:genetics / Q000502:physiology*; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism; D017629:Gap Junctions / Q000235:genetics / Q000502:physiology*; D015603:Keratinocytes / Q000378:metabolism / Q000502:physiology; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D010212:Papilloma / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D012878:Skin Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*
D015820:Cadherins; D018031:Connexin 43; D009363:Neoplasm Proteins