Connexin expression in epidermal cell lines from SENCAR mouse skin tumors

Abstract

Alteration of gap-junctional intercellular communication (GJIC) has long been proposed to be involved in carcinogenesis. Previously, we reported that the level of gap junctional intercellular communication in mouse skin carcinoma cell lines is significantly lower than in papilloma cell lines and normal mouse keratinocytes Klann et al., Cancer Res 49:699-705, 1989). Here, we present data on expression of the gap-junctional protein connexins (Cx) 26, Cx31.1, and Cx43 in a comprehensive panel of keratinocyte cell lines representing different stages of mouse skin carcinogenesis and the effect of different conditions of propagation on Cx phenotype. Northern and western blot analyses and immunostaining showed that all cell lines studied in vitro expressed Cx43 but most did not express Cx31.1 or Cx26. The abundance of Cx43 expression on plasma membranes correlated well with the level of GJIC. In vivo expression of Cx43 and Cx26 was strongly increased. Whereas none of tumorigenic cell lines expressed Cx26 gap junctions in culture, those growing as tumors in nude mice began to express Cx26 protein. The comparison of Cx expression on the keratinocyte membranes in three different groups of tumors (papillomas and squamous cell and spindle cell carcinomas) clearly revealed that the abundance of Cx43 and Cx26 expression directly correlated with the level of tumor differentiation. All studied tumors were Cx31.1 negative. These results suggest that both Cx expression and gap-junction permeability are gradually reduced during the tumor progression stage of mouse skin carcinogenesis.

Connexins: a connection with the skin

“…Tumor progression, including the loss of differentiation, invasion, and metastasis, is associated with a quantitative and qualitative gradual decrease in expression of Cx43, Cx26, and Cx31.1 during multistage mouse skin carcinogenesis. Analysis of the expression pattern and gap junctional permeability in this model system suggests a differential regulation of each Cx gene during tumorigenesis, the mechanisms of which are still largely unknown (71,83,85). Recent data point to a possible inactivation of Cxs by hypermethylation of their promotor region, aberrant intracellular localization, or alternatively, disruption of various functional control mechanisms (86) (89)(90)(91).…”

Cx31.1 acts as a tumour suppressor in non‐small cell lung cancer (NSCLC) cell lines through inhibition of cell proliferation and metastasis

“…reported that Cx31.1 was down‐regulated in head and neck squamous cell carcinoma [25]. Budunova et al found that all the epidermal cell lines from SENCAR mouse skin tumours they studied were Cx31.1 negative [26]. To our knowledge, there is no report about the association between Cx31.1 and lung cancer carcinogenesis and metastasis as yet.…”

Cellular sublocalization of Cx43 and the establishment of functional coupling in IMR-32 neuroblastoma cells

“…This is in accordance with the Neigborhood Coherence Principle (NCP), described by Phipps et al [67,68], which suggests that a system of interacting cells can produce and maintain homeostasis by virtue of cell‐cell communication. In support of the NCP, several studies have shown that any decrease or disconnection in GJIC would allow some cells with proliferative potential to resume their mitotic activity [15,69–74]. This proliferative potential is associated with the lack of differentiation, which is one of the hallmarks of NB [9].…”