Changes in gap junctional connexin isoforms during prostate cancer progression.
BACKGROUND
Connexins have their traditional function as part of gap junction (GJ) structures, but have recently been shown to have GJ-independent roles. Although GJs and their connexin subunits are thought to be down-regulated in cancer, depending on the connexin examined, many times the expression level is preserved or even increased. This is further apparent by the importance of GJs in "bystander effects" of radiation and viral targeting treatments.


METHODS
We surveyed connexin isoforms in prostate cancer cell lines and tissue with RT-PCR and immunohistochemistry. Upon modulating GJ function, we observed prostate epithelial cell behaviors.


RESULTS
Advanced cells within PC-3 and LNCaP prostate cancer progression models exhibit elevated connexin 26 (Cx26) levels-a trend validated in clinical samples. When GJs were inhibited, adhesion was not affected, but invasion and migration were strikingly decreased. A link between the expression of Cx26 and integrin adhesion-linked functions are suggested by Cx26's direct interaction with focal adhesion kinase (FAK).


CONCLUSIONS
These results suggest a novel mechanism for adhesion regulation by a GJ-independent Cx26 function that correlates with prostate disease progression. The increased Cx26 expression during prostate cancer progression plays a role in adhesion regulation possibly through its interaction with FAK.
Tate
Amanda W
AW
Department of Urology, Molecular Urology and Therapeutics Program, Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Lung
Tina
T
Radhakrishnan
Anu
A
Lim
So Dug
SD
Lin
Xi
X
Edlund
Magnus
M
D002448:Cell Adhesion; D002455:Cell Division; D045744:Cell Line, Tumor; D002465:Cell Movement; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics* / Q000378:metabolism*; D018450:Disease Progression; D017629:Gap Junctions / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009924:Organ Culture Techniques; D011471:Prostatic Neoplasms / Q000473:pathology*; D020033:Protein Isoforms / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017630:Connexins; C000607042:GJB2 protein, human; D020033:Protein Isoforms; D000072259:Connexin 26