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Down regulation of 3p genes, LTF, SLC38A3 and DRR1 , upon growth of human chromosome 3–mouse fibrosarcoma hybrids in severe combined immunodeficiency mice
Author(s) -
Kholodnyuk Irina D.,
Kozireva Svetlana,
KostAlimova Maria,
Kashuba Vladimir,
Klein George,
Imreh Stefan
Publication year - 2006
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.21794
Subject(s) - biology , gene , fhit , fibrosarcoma , gene expression , microbiology and biotechnology , chromosome , cancer research , genetics , tumor suppressor gene , carcinogenesis
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 ( DRR1 ) gene at 3p14.2 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. © 2006 Wiley‐Liss, Inc.