Genetic analysis of high-metastatic clone of RCT sarcoma in mice, and its growth regression in vivo in response to angiogenesis inhibitor TNP-470.
Genetic analysis of a high-metastatic clone of RCT sarcoma (HM-RCT) was the aim of the study. HM-RCT was developed by the lung passage as well as limiting dilution method from the original RCT sarcoma, in which a tumor was spontaneously developed in a C3H/He mouse. HM-RCT expressed enhanced POU domain (class 2, associating factor 1), adenylate cyclase 7, procollagen type III (alpha), A kinase anchor protein 4 and Ehm (expressed on high-metastatic cells) and 11 expressed sequence tags (ESTs). compared with the original clone of RCT. Eighteen specific genes and 14 ESTs were underexpressed in HM-RCT. We investigated the effects of angiogenesis inhibitor TNP-470 on tumor growth and metastasis of this HM-RCT in vivo. In an experimental group, mice received TNP-470 (30 mg/kg) intraperitoneally every other day. After 5 weeks, the growth of the TNP-470-treated tumor was significantly suppressed in vivo, but did not affect the metastasis. The proportion of positive PCNA-stained cells and cellular telomerase activity was significantly low in response to TNP-470.
Kanamori
M
M
Department of Orthopaedic Surgery, University of Toyama, Toyama, Japan. kanamori@med.u-toyama.ac.jp
Yasuda
T
T
Ohmori
K
K
Nogami
S
S
Aoki
M
M
D054758:A Kinase Anchor Proteins; D000262:Adenylyl Cyclases / Q000235:genetics / Q000378:metabolism; D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism; D003510:Cyclohexanes / Q000494:pharmacology* / Q000627:therapeutic use; D020224:Expressed Sequence Tags; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D020411:Oligonucleotide Array Sequence Analysis; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D012513:Sarcoma, Experimental / Q000098:blood supply / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012717:Sesquiterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D019098:Telomerase / Q000378:metabolism; D013997:Time Factors; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
D054758:A Kinase Anchor Proteins; C485479:Akap4 protein, mouse; D020533:Angiogenesis Inhibitors; D024061:Collagen Type III; D003510:Cyclohexanes; C490424:Pou2af1 protein, mouse; D018809:Proliferating Cell Nuclear Antigen; D011498:Protein Precursors; D012717:Sesquiterpenes; D015534:Trans-Activators; D019098:Telomerase; D000262:Adenylyl Cyclases; D000077609:O-(Chloroacetylcarbamoyl)fumagillol