title: Differential expression of CHL1 gene during development of major human cancers.
abstract: BACKGROUND
  CHL1 gene (also known as CALL) on 3p26.3 encodes a one-pass trans-membrane cell adhesion molecule (CAM). Previously CAMs of this type, including L1, were shown to be involved in cancer growth and metastasis.
  
  
  RESULTS
  We used Clontech Cancer Profiling Arrays (19 different types of cancers, 395 samples) to analyze expression of the CHL1 gene. The results were further validated by RT-qPCR for breast, renal and lung cancer. Cancer Profiling Arrays revealed differential expression of the gene: down-regulation/silencing in a majority of primary tumors and up-regulation associated with invasive/metastatic growth. Frequent down-regulation (>40% of cases) was detected in 11 types of cancer (breast, kidney, rectum, colon, thyroid, stomach, skin, small intestine, bladder, vulva and pancreatic cancer) and frequent up-regulation (>40% of cases)--in 5 types (lung, ovary, uterus, liver and trachea) of cancer. Using real-time quantitative PCR (RT-qPCR) we found that CHL1 expression was decreased in 61% of breast, 60% of lung, 87% of clear cell and 89% papillary renal cancer specimens (P<0.03 for all the cases). There was a higher frequency of CHL1 mRNA decrease in lung squamous cell carcinoma compared to adenocarcinoma (81% vs. 38%, P = 0.02) without association with tumor progression.
  
  
  CONCLUSIONS
  Our results suggested that CHL1 is involved in the development of different human cancers. Initially, during the primary tumor growth CHL1 could act as a putative tumor suppressor and is silenced to facilitate in situ tumor growth for 11 cancer types. We also suggested that re-expression of the gene on the edge of tumor mass might promote local invasive growth and enable further metastatic spread in ovary, colon and breast cancer. Our data also supported the role of CHL1 as a potentially novel specific biomarker in the early pathogenesis of two major histological types of renal cancer.
authors.affiliation: Laboratory of Structural and Functional Genomics, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Vera N
authors.initials: VN
authors.lastname: Senchenko
authors.forename: George S
authors.initials: GS
authors.lastname: Krasnov
authors.forename: Alexey A
authors.initials: AA
authors.lastname: Dmitriev
authors.forename: Anna V
authors.initials: AV
authors.lastname: Kudryavtseva
authors.forename: Ekaterina A
authors.initials: EA
authors.lastname: Anedchenko
authors.forename: Eleonora A
authors.initials: EA
authors.lastname: Braga
authors.forename: Irina V
authors.initials: IV
authors.lastname: Pronina
authors.forename: Tatiana T
authors.initials: TT
authors.lastname: Kondratieva
authors.forename: Sergey V
authors.initials: SV
authors.lastname: Ivanov
authors.forename: Eugene R
authors.initials: ER
authors.lastname: Zabarovsky
authors.forename: Michael I
authors.initials: MI
authors.lastname: Lerman
mesh_terms: D015815:Cell Adhesion Molecules; D045744:Cell Line, Tumor; D019295:Computational Biology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D011230:Precancerous Conditions / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C490650:CHL1 protein, human; D015815:Cell Adhesion Molecules; D008565:Membrane Proteins; D012333:RNA, Messenger