Overexpression of AQP5, a putative oncogene, promotes cell growth and transformation.
Overexpression of several aquaporins has been reported in different types of human cancer but the role of AQPs in human carcinogenesis has not yet been clearly defined. Here, we demonstrate that ectopic expression of human AQP5 (hAQP5), a water channel expressed in lung, salivary glands, and kidney, induces many phenotypic changes characteristic of transformation both in vitro and in vivo. Furthermore, the cell proliferative ability of AQP5 appears to be dependent upon the phosphorylation of a cAMP-protein kinase (PKA) consensus site located in a cytoplasmic loop of AQP5. In addition, phosphorylation of the PKA consensus site was found to be phosphorylated preferentially in tumors. These findings altogether indicate that hAQP5 plays an important role in human carcinogenesis and, furthermore, provide an attractive therapeutic target.
Woo
Janghee
J
Department of Otolaryngology - Head and Neck Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Lee
Juna
J
Chae
Young Kwang
YK
Kim
Myoung Sook
MS
Baek
Jin Hyen
JH
Park
Jong Chul
JC
Park
Min Joo
MJ
Smith
Ian M
IM
Trink
Barry
B
Ratovitski
Edward
E
Lee
Taekyul
T
Park
Bumsoo
B
Jang
Se Jin
SJ
Soria
Jean C
JC
Califano
Joseph A
JA
Sidransky
David
D
Moon
Chulso
C
D000818:Animals; D051402:Aquaporin 5 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000187:drug effects / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D015854:Up-Regulation / Q000235:genetics
C496036:AQP5 protein, human; D051402:Aquaporin 5; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering