Inactivation of human SRBC, located within the 11p15.5-P15.4 tumor suppressor region, in breast and lung cancers

X. L. Xu, L. C. Wu, F. Du, A. Davis, M. Peyton, Y. Tomizawa, A. Maitra, Gail Tomlinson, A. F. Gazdar, B. E. Weissman, A. M. Bowcock, R. Baer, J. D. Minna

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Abstract

A cDNA clone encoding human SRBC [serum deprivation response factor (sdr)-related gene product that binds to c-kinase] was isolated in a yeast two-hybrid screening, with amino acids 1-304 of BRCA1 as the probe. The human SRBC gene (hSRBC) was mapped to chromosome region 11p15.5-p15.4, close to marker D11S1323, at which frequent loss of heterozygosity (LOH) has been observed in sporadic breast, lung, ovarian, and other types of adult cancers as well as childhood tumors, hSRBC-coding region mutations including frame shift and truncation mutations were detected in a few ovarian and lung cancer cell lines. More significantly, the expression of hSRBC protein was down-regulated in a large fraction [30 (70%) of 43] of breast, lung, and ovarian cancer cell lines, whereas strong expression of hSRBC protein was detected in normal mammary and lung epithelial cells. The down-regulation of hSRBC expression in cancer cells was associated with hypermethylation of CpG dinucleotides in its promoter region, and 3 (60%) of 5 primary breast tumors and 11 (79%) of 14 primary lung tumors were also found to be hypermethylated. Treatment of breast cancer MCF7 cells with 5′azacytidine and Trichostatin A resulted in expression of hSRBC, confirming DNA methylation as the mode of inactivation. Our results suggest that epigenetic or mutational inactivation of hSRBC may contribute to the pathogenesis of several types of human cancers, marking hSRBC as a candidate tumor suppressor gene.

Original languageEnglish (US)
Pages (from-to)7943-7949
Number of pages7
JournalCancer Research
Volume61
Issue number21
StatePublished - Nov 1 2001
Externally publishedYes

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Lung Neoplasms
Breast Neoplasms
Neoplasms
Genes
Ovarian Neoplasms
Lung
trichostatin A
Breast
Serum Response Factor
Cell Line
Frameshift Mutation
Loss of Heterozygosity
MCF-7 Cells
DNA Methylation
Tumor Suppressor Genes
Genetic Promoter Regions
Epigenomics
Proteins
Phosphotransferases
Down-Regulation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Xu, X. L., Wu, L. C., Du, F., Davis, A., Peyton, M., Tomizawa, Y., ... Minna, J. D. (2001). Inactivation of human SRBC, located within the 11p15.5-P15.4 tumor suppressor region, in breast and lung cancers. Cancer Research, 61(21), 7943-7949.

Inactivation of human SRBC, located within the 11p15.5-P15.4 tumor suppressor region, in breast and lung cancers. / Xu, X. L.; Wu, L. C.; Du, F.; Davis, A.; Peyton, M.; Tomizawa, Y.; Maitra, A.; Tomlinson, Gail; Gazdar, A. F.; Weissman, B. E.; Bowcock, A. M.; Baer, R.; Minna, J. D.

In: Cancer Research, Vol. 61, No. 21, 01.11.2001, p. 7943-7949.

Research output: Contribution to journalArticle

Xu, XL, Wu, LC, Du, F, Davis, A, Peyton, M, Tomizawa, Y, Maitra, A, Tomlinson, G, Gazdar, AF, Weissman, BE, Bowcock, AM, Baer, R & Minna, JD 2001, 'Inactivation of human SRBC, located within the 11p15.5-P15.4 tumor suppressor region, in breast and lung cancers', Cancer Research, vol. 61, no. 21, pp. 7943-7949.
Xu XL, Wu LC, Du F, Davis A, Peyton M, Tomizawa Y et al. Inactivation of human SRBC, located within the 11p15.5-P15.4 tumor suppressor region, in breast and lung cancers. Cancer Research. 2001 Nov 1;61(21):7943-7949.
Xu, X. L. ; Wu, L. C. ; Du, F. ; Davis, A. ; Peyton, M. ; Tomizawa, Y. ; Maitra, A. ; Tomlinson, Gail ; Gazdar, A. F. ; Weissman, B. E. ; Bowcock, A. M. ; Baer, R. ; Minna, J. D. / Inactivation of human SRBC, located within the 11p15.5-P15.4 tumor suppressor region, in breast and lung cancers. In: Cancer Research. 2001 ; Vol. 61, No. 21. pp. 7943-7949.
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abstract = "A cDNA clone encoding human SRBC [serum deprivation response factor (sdr)-related gene product that binds to c-kinase] was isolated in a yeast two-hybrid screening, with amino acids 1-304 of BRCA1 as the probe. The human SRBC gene (hSRBC) was mapped to chromosome region 11p15.5-p15.4, close to marker D11S1323, at which frequent loss of heterozygosity (LOH) has been observed in sporadic breast, lung, ovarian, and other types of adult cancers as well as childhood tumors, hSRBC-coding region mutations including frame shift and truncation mutations were detected in a few ovarian and lung cancer cell lines. More significantly, the expression of hSRBC protein was down-regulated in a large fraction [30 (70{\%}) of 43] of breast, lung, and ovarian cancer cell lines, whereas strong expression of hSRBC protein was detected in normal mammary and lung epithelial cells. The down-regulation of hSRBC expression in cancer cells was associated with hypermethylation of CpG dinucleotides in its promoter region, and 3 (60{\%}) of 5 primary breast tumors and 11 (79{\%}) of 14 primary lung tumors were also found to be hypermethylated. Treatment of breast cancer MCF7 cells with 5′azacytidine and Trichostatin A resulted in expression of hSRBC, confirming DNA methylation as the mode of inactivation. Our results suggest that epigenetic or mutational inactivation of hSRBC may contribute to the pathogenesis of several types of human cancers, marking hSRBC as a candidate tumor suppressor gene.",
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AU - Davis, A.

AU - Peyton, M.

AU - Tomizawa, Y.

AU - Maitra, A.

AU - Tomlinson, Gail

AU - Gazdar, A. F.

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AU - Baer, R.

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