title: Role of two types of angiotensin II receptors in colorectal carcinoma progression.
abstract: Angiotensin II (Ang-II) is a bioactive peptide associated closely with the progression and metastasis of colorectal cancer (CRC). We examined the expression and role of 2 Ang-II receptor types in 20 cases of CRC. Ang-II type 1 receptor (AT1R) protein was localized to the plasma membrane, whereas Ang-II type 2 receptor (AT2R) protein was localized to the nuclei. AT1R expression showed a direct correlation with tumor stage and liver metastasis, whereas AT2R expression showed an inverse correlation. A knockdown study of the AT1R or AT2R with Ang-II treatment was performed to reveal their individual roles in a mouse rectal cell line CMT93, which expresses both Ang-II receptor types. AT2R knockdown showed that the AT1R was associated with tumor growth, survival, invasion and VEGF-A secretion in CMT93 cells in a dose-dependent manner. In contrast, AT1R knockdown showed that the AT2R was associated with increased VEGF-A secretion at low Ang-II concentrations, whereas high concentrations of Ang-II inhibited tumor growth, survival, invasion and VEGF-A secretion. Thus, the AT1R showed a monophasic protumoral effect, while the AT2R showed a biphasic amphitumoral effect. Our findings suggest that a high angiotensinogen condition in the liver might evoke the antitumoral role of the AT2R in CRC cells.
authors.affiliation: Department of Molecular Pathology, Nara Medical University, Kashihara, Japan.
authors.forename: Linyan
authors.initials: L
authors.lastname: Zhou
authors.forename: Yi
authors.initials: Y
authors.lastname: Luo
authors.forename: Seiya
authors.initials: S
authors.lastname: Sato
authors.forename: Eriko
authors.initials: E
authors.lastname: Tanabe
authors.forename: Misaho
authors.initials: M
authors.lastname: Kitayoshi
authors.forename: Rina
authors.initials: R
authors.lastname: Fujiwara
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Sasaki
authors.forename: Kiyomu
authors.initials: K
authors.lastname: Fujii
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ohmori
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kuniyasu
mesh_terms: D000368:Aged; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000648:ultrastructure; D018450:Disease Progression; D005260:Female; D055786:Gene Knockout Techniques; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary; D008297:Male; D051379:Mice; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism*; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics / Q000378:metabolism*
chemical_list: C544065:AGTR1 protein, human; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II