Connexin 26
(Cx26)

Gap junction protein, beta-2 (GJB2)
Gap junction protein, 26-kD

Gene: GJB2 maps to 13q11-q12 (Mignon C. et al., 1996).
mRNA: size:
Protein:

Alteration of gap junctional intercellular communication (GJIC) is among the early changes associated with carcinogenesis and restoration of gap junctions can suppress tumor cell growth.
GJIC mediates the transfer of ions, nucleotides, and small regulatory molecules from cytoplasm to cytoplasm without leakage into the extracellular space.
Gap junctions are composed of multiple hemichannels (connexons) in the plasma membrane of one cell joined in mirror symmetry with the same number of hemichannels in the apposing cell membrane. Connexons are formed by members of a multigene family of distinct but functionnally related proteins called connexins (Cxs).
Gap junctions are dynamic structures with relatively short half-lives of 1-5 h. They are tightly regulated by voltage, growth factors, a number of secondary messengers including cAMP and retinoids and are subjected to phosphorylation by a number of protein kinases.
While at least 15 Cxs genes have been identified in mammalian cells, expression of three of them (Cx43, Cx26, Cx32) has been detected in normal breast tissue. Cx43 is the predominant Cx in human breast epithelium, and it was detected predominantly between myo-epithelial cells (Monaghan P. et al., 1996). There is evidence suggesting that Cxs may play a role in normal mammmogenesis, lactogenesis, and involution. It has been shown that Cx26 levels in the epithelium increase substantially in the lactating mouse mammary gland epithelium and decline during involution, and hormones such as estrogens and progesterones have been shown to regulate the expression of the Cx43 gene.

Cell lines:
- mRNA expression of genes from normal and tumor-derived human mammary epithelial cells was compared by subtractive hybridization. Among the isolated clones were genes encoding Cx26 and GST-pi (Lee S.W. et al., 1991).

Tumors:
- The immunocytochemical expression of Cx26 and Cx43 was studied in normal human breast, 11 benign breast lesions, two special-type carcinomas, and 27 invasive carcinomas of no special histological type (NST). Cx26 generally was not expressed at detectable level in normal human breast, but punctate Cx43 immunostaining of the myoepithelial cells was found. Cx43 staining of the myoepithelium was also a feature of the benign lesions and ductal carcinoma in situ (DCIS). In general, the epithelial cells of benign lesions failed to stain for either connexin. Similarly, a lobular carcinoma did not express Cx26 or Cx43, but there was punctate Cx43 in the epithelial cells of a mucoid carcinoma. Cx26 was up-regulated in the carcinoma cells of 15 of the 27 invasive NST carcinomas, although the staining was usually cytoplasmic and heterogeneous. Cx43 was expressed by stromal cells, possibly myofibroblasts, in all NST carcinomas. Furthermore, there was heterogeneous Cx43 expression in the carcinoma cells of 14 of the 27 NST carcinomas and the staining was often intercellular and punctate, characteristic of functional connexins (Jamieson S. et al., 1998).

Jamieson S. et al. (1998) Expression of gap junction proteins connexin 26 and connexin 43 in normal human breast and in breast tumours. J. Pathol. 184, 37-43. (PubMed)
Lee S.W. et al. (1991) Positive selection of candidate tumor-suppressor genes by subtractive hybridization. Proc. Natl. Acad. Sci. USA 88, 2825-2829. (PubMed)
Mignon C. et al. (1996) Assignment of connexin 26 (GJB2) and 46 (GJA3) genes to human chromosome 13q11-q12 and mouse chromosome 14D1-E1 by in situ hybridization. Cytogenet. Cell Genet. 72, 185-186. (PubMed)
Wilgenbus K.K. et al. (1992) Expression of Cx26, Cx32 and Cx43 gap junction proteins in normal and neoplastic human tissues. Int. J. Cancer 51, 522-529. (PubMed)

Under construction