title: Up-regulated expression of l-caldesmon associated with malignancy of colorectal cancer.
abstract: BACKGROUND
  Caldesmon (CaD), a major actin-associated protein, is found in smooth muscle and non-muscle cells. Smooth muscle caldesmon, h-CaD, is a multifunctional protein, and non-muscle cell caldesmon, l-CaD, plays a role in cytoskeletal architecture and dynamics. h-CaD is thought to be an useful marker for smooth muscle tumors, but the role(s) of l-CaD has not been examined in tumors.
  
  
  METHODS
  Primary colon cancer and liver metastasis tissues were obtained from colon cancer patients. Prior to chemoradiotherapy (CRT), normal and cancerous tissues were obtained from rectal cancer patients. Whole-tissue protein extracts were analyzed by 2-DE-based proteomics. Expression and phosphorylation level of main cellular signaling proteins were determined by western blot analysis. Cell proliferation after CaD siRNA transfection was monitored by MTT assay.
  
  
  RESULTS
  The expression level of l-CaD was significantly increased in primary colon cancer and liver metastasis tissues compared to the level in the corresponding normal tissues. In cancerous tissues obtained from the patients showing poor response to CRT (Dworak grade 4), the expression of l-CaD was increased compared to that of good response group (Dworak grade 1). In line with, l-CaD positive human colon cancer cell lines were more resistant to 5-fluorouracil (5-FU) and radiation treatment compared to l-CaD negative cell lines. Artificial suppression of l-CaD increased susceptibility of colon cancer cells to 5-FU, and caused an increase of p21 and c-PARP, and a decrease of NF-kB and p-mTOR expression.
  
  
  CONCLUSIONS
  Up-regulated expression of l-CaD may have a role for increasing metastatic property and decreasing CRT susceptibility in colorectal cancer cells.
authors.affiliation: Colorectal Cancer Branch, Division of Translational and Clinical Research I, Research Institute, National Cancer Center, Goyang, 410-769, Republic of Korea.
authors.forename: Kyung-Hee
authors.initials: KH
authors.lastname: Kim
authors.forename: Seung-Gu
authors.initials: SG
authors.lastname: Yeo
authors.forename: Won Ki
authors.initials: WK
authors.lastname: Kim
authors.forename: Dae Yong
authors.initials: DY
authors.lastname: Kim
authors.forename: Hyun Yang
authors.initials: HY
authors.lastname: Yeo
authors.forename: Jun Pyu
authors.initials: JP
authors.lastname: Hong
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Chang
authors.forename: Ji Won
authors.initials: JW
authors.lastname: Park
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Byung Chang
authors.initials: BC
authors.lastname: Kim
authors.forename: Byong Chul
authors.initials: BC
authors.lastname: Yoo
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000378:metabolism* / Q000502:physiology; D015153:Blotting, Western; D002148:Calmodulin-Binding Proteins / Q000378:metabolism* / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D034741:RNA, Small Interfering; D015854:Up-Regulation
chemical_list: D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; D002148:Calmodulin-Binding Proteins; D034741:RNA, Small Interfering