Carbonic anhydrase-related protein VIII promotes colon cancer cell growth.
Increased expression of carbonic anhydrase-related protein (CA-RP) VIII has previously been shown in colorectal carcinoma. Since CA-RP has no catalytic carbonic anhydrase (CA) activity, the present study attempted to elucidate its biological significance in colon cancer cells. From a colon cancer cell line (LoVo), we established clones that overexpressed CA-RP VIII (LoVo-CA8) and a control transfectant with a vector alone (LoVo-pCIneo) and studied alterations in the biological behaviors of the tumor cells both in vitro and in vivo. LoVo-CA8 cells showed significantly increased mRNA and protein expressions of CA-RP VIII as compared to LoVo-pCIneo cells. Cell proliferation, colony formation, and cell invasion assays showed that LoVo-CA8 cells had significantly higher cell proliferative and invasive abilities as compared to parental LoVo and LoVo-pCIneo cells in vitro. In an in vivo xenograft assay, LoVo-CA8 cells showed a higher tumor growth rate than parental LoVo cells. Further, small interfering RNA (siRNA)-mediated knockdown of CA-RP VIII revealed significant inhibition in cell proliferation and colony formation of a colon cancer cell line HCT116, which showed high endogenous expression of CA-RP VIII. These findings indicated that CA-RP VIII plays a role in the growth of colon cancer cells.
Nishikata
Makoto
M
Department of Gastroenterology and Hepatology, Kochi Medical School, Nankoku, Kochi, Japan.
Nishimori
Isao
I
Taniuchi
Keisuke
K
Takeuchi
Tamotsu
T
Minakuchi
Tomoko
T
Kohsaki
Takuhiro
T
Adachi
Yoshihiro
Y
Ohtsuki
Yuji
Y
Onishi
Saburo
S
D000818:Animals; D014408:Biomarkers, Tumor / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D003114:Colony-Forming Units Assay; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D002256:Carbonic Anhydrases; D047908:Intracellular Signaling Peptides and Proteins
D014408:Biomarkers, Tumor; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D034741:RNA, Small Interfering; C512821:Car8 protein, mouse; D002256:Carbonic Anhydrases; C512818:CA8 protein, human; D047908:Intracellular Signaling Peptides and Proteins