Reduced expression of multiple gap junction proteins is a feature of cervical dysplasia

Connexins, a family of 20 trans-membrane proteins in humans, comprise the main subunits of gap junctions – specialised clusters of intercellular channels that allow adjacent cells to directly share ions and hydrophilic molecules of up to ~1 KDa in size [1]. Gap junctional intercellular communication (GJIC) is thought to control tissue homeostasis and to coordinate cellular processes such as proliferation, migration and differentiation. Disruption of GJIC or mutations in connexins is associated with several human diseases such as hearing loss, neuropathies and various skin conditions [2].There is also substantial evidence that connexins have a tumour suppressor role [reviewed in [3]]. While reduced or aberrant GJIC or connexin expression has been found in some tumours and in many tumour cell lines [4-7], restoration of GJIC in tumour cell lines by connexin transfection can reduce growth and tumourigenicity [8-10]. However, the tumour suppressive effects may be tissue and connexin-specific [11,12] and also appear to involve non-gap junctional properties of connexins [13-15]. Moreover, it has been observed that connexin expression (especially connexin26) is often upregulated in hyperplastic tissues including psoriatic epidermis and viral warts [16], benign prostatic hyperplasia [17], and mouse papillomas [18]. While induction of connexin26 and connexin43 has also been observed in metastatic breast carcinomas [19], others have reported that connexin26 and connexin43 are downregulated in mammary carcinoma cell lines and re-expression of these connexins leads to repression of tumour-forming ability [20]. Although potent tumour promoters markedly downregulate GJIC in cultured cells [21], intact skin painted with tumour promoters such as 12-O-tetradecanoylphorbol 13-acetate (TPA) show a dramatic upregulation of connexin26 and connexin43 expression [22-24]. Moreover, several reports have shown a negative correlation between expression of connexins and cell diapedesis and or