Aquaporin 1 is overexpressed in lung cancer and stimulates NIH-3T3 cell proliferation and anchorage-independent growth.
The aquaporins represent a family of transmembrane water channel proteins that play a major role in trans-cellular and transepithelial water movement. Most tumors have been shown to exhibit high vascular permeability and interstitial fluid pressure, but the transport pathways for water within tumors remain unknown. Here, we tested 10 non-small cell lung cancer cell lines of various origins by reverse transcriptase-polymerase chain reaction and Western blot analysis and identified clear expression of aquaporin 1 (AQP1) in seven cell lines. We next examined the distribution of the AQP1 protein in several types of primary lung tumors (16 squamous cell carcinomas, 21 adenocarcinomas, and 7 bronchoalveolar carcinomas) by immunohistochemical staining. AQP1 was overexpressed in 62% (13 of 21) and 75% (6 of 8) of adenocarcinoma and bronchoalveolar carcinoma, respectively, whereas all cases of squamous cell carcinoma and normal lung tissue were negative. Forced expression of full-length AQP1 cDNA in NIH-3T3 cells induced many phenotypic changes characteristic of transformation, including cell proliferation-enhancing activity by the MTT assay and anchorage-independent growth in soft agar. Although further details on the molecular function of AQP1 related to tumorigenesis remain to be elucidated, our results suggest a potential role of AQP1 as a novel therapeutic target for the management of lung cancer.
The Head and Neck Cancer Research Division, Department of Otolaryngology, The Johns Hopkins School of Medicine, 818 Ross Research Building, 720 Rutland Ave., Baltimore, MD 21205-2196, USA.
Mohammad Obaidul
MO
Hoque
Jean-Charles
JC
Soria
Janghee
J
Woo
Taekyeol
T
Lee
Juna
J
Lee
Se Jin
SJ
Jang
Sunil
S
Upadhyay
Barry
B
Trink
Constance
C
Monitto
Chantal
C
Desmaze
Li
L
Mao
David
D
Sidransky
Chulso
C
Moon
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000818:Animals; D051398:Aquaporin 1 / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D041681:NIH 3T3 Cells
D051398:Aquaporin 1