Down regulation of 3p genes, LTF, SLC38A3 and DRR1, upon growth of human chromosome 3-mouse fibrosarcoma hybrids in severe combined immunodeficiency mice

Irina D. Kholodnyuk, Svetlana Kozireva, Maria Kost-Alimova, Vladimir Kashuba, George Klein, Stefan Imreh

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)

Abstract

We have applied a functional test for tumour antagonizing genes based on human chromosome 3 (chr3)-mouse fibrosarcoma A9 MCHs that were studied in vitro and after growth as tumours in severe combined immunodeficiency (SCID) mice. Previously, we reported that 9 out of the 36 SCID-tumours maintained the transferred chr3 ("chr3+" tumours), but lost the expression of the known human TSG fragile histidine triad gene (FHIT) in contrast to 14 other 3p-genes examined. Here we report the results of the duplex RT-PCR analysis of 9 "chr3+" tumours and 3 parental MCHs. We have examined the expression of 34 human 3p-genes from known cancer-related regions of instability, including 13 genes from CER1 defined by us previously at 3p21.33-p21.31 and 10 genes from the LUCA region at 3p21.31. We have found that in addition to FHIT, expression of the LTF gene from CER1 at 3p21.33-p21.31 was lost in all 9 tumours analyzed. The transcript of the solute carrier family 38 member 3 gene (SLC38A3) gene from LUCA region at 3p21.31 was not found in 8 and was greatly reduced in 1 out of these 9 tumours. Expression of the down-regulated in renal cell carcinoma gene (DRRl) gene at 3pl4.2 was lost in 7 and down regulated in 2 "chr3+" tumours. In the SCID-tumour derived cell lines treatment with 5-aza-2′-deoxycytidine restored the mRNA expression of LTF, indicating the integrity of DNA sequences. Notably that transcription of the LTF and 2 flanking genes, LRRC2 and TMEM7, as well as transcription of the SLC38A3 gene, were also impaired in all 5 RCC cell lines analyzed. Our data indicate these genes as putative tumour suppressor genes.

Original languageEnglish
Pages (from-to)99-107
Number of pages9
JournalInternational Journal of Cancer
Volume119
Issue number1
DOIs
Publication statusPublished - 1 Jul 2006

Keywords*

  • Human chromosome 3 genes
  • Microcell hybrid
  • SCID tumours

Field of Science*

  • 3.2 Clinical medicine

Publication Type*

  • 1.1. Scientific article indexed in Web of Science and/or Scopus database

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