DBC2 , a candidate for a tumor suppressor gene involved in breast cancer

Abstract

A previously uncharacterized gene, DBC2 (deleted in breast cancer), was cloned from a homozygously deleted region at human chromosome 8p21. DBC2 contains a highly conserved RAS domain and two putative protein interacting domains. Our analyses indicate that DBC2 is the best candidate tumor suppressor gene from this region. It lies within the epicenter of the deletions and is homozygously deleted in 3.5% (7͞200) of breast tumors. Mutation analysis of DBC2 led to discovery of two instances of somatic missense mutations in breast tumor specimens, whereas no missense mutations were found in other candidates from the region. Unlike other genes in the region, expression of DBC2 is often extinguished in breast cancer cells or tissues. Moreover, our functional analysis revealed that DBC2 expression in breast cancer cells lacking DBC2 transcripts causes growth inhibition. By contrast, expression of a somatic mutant discovered in a breast cancer specimen does not suppress the growth of breast cancer cells.

Recurrent genomic aberrations combined with deletions of various tumour suppressor genes may deregulate the G1/S transition in CD4+CD56+ haematodermic neoplasms and contribute to the aggressiveness of the disease

“…These deletions involve many genes that were earlier reported to be frequently lost by deletion, mutation or promoter methylation events in various solid tumours and acute leukaemia, such as ETV6 (12p13), SLIT2(4p15), AUTS2(7q11), NF1(17q12), MSH5 (6p21), MSH3(5q), HUS1(7p12), CDKN2D(19p13.2), WISP-1(8q24), IDE or TLX2(2p13.1). 14,[16][17][18][19][20][21][22][23][24] These genes are involved in major cellular processes, including DNA repair (MSH3, MSH5, HUS1), cell cycle regulation (HUS1, CDKN2D) and the RAS pathway (NF1). Another gene, IDE (10q32), a putative tumour suppressor insulin degrading enzyme, may play a role as a RB protector by preventing inactivation of RB1.…”

Negative regulation of the deacetylase SIRT1 by DBC1

“…1b, Gi: 24432106). The DBC1 gene was initially identified as it is localized to a region of chromosome 8p21 that was homozygously deleted in human breast cancer; however, the molecular function of DBC1 is poorly understood 18,19 .To examine the interaction between endogenous DBC1 and SIRT1, cell extracts from human osteosarcoma U2OS cells were immunoprecipitated with the anti-SIRT1 antibody or with the …”

“…1b, Gi: 24432106). The DBC1 gene was initially identified as it is localized to a region of chromosome 8p21 that was homozygously deleted in human breast cancer; however, the molecular function of DBC1 is poorly understood 18,19 .…”

Loss of DBC2 Expression is an Early and Progressive Event in the Development of Lung Adenocarcinoma

“…Many mutations, especially those involving recessive oncogenes, have been described in invasive lung carcinomas (Akita, 2004). Hamaguchi et al have found a novel tumor suppression gene named Deleted in Breast Cancer 2 (DBC2) in human chromosome 8p21, which belonged to the RhoBTB family (Hamaguchi et al, 2002). Recent researches indicate that DBC2 participates in diverse cellular activities, significantly influences cellcycle, apoptosis, cytoskeleton and membrane-trafficking pathways (Siripurapu et al, 2005;Chang et al, 2006).…”

“…Recently, DBC2 is isolated as a tumor suppressor gene from human chromosome 8p21, and it is the best candidate tumor suppressor gene from this region (Hamaguchi et al, 2002). Incidence of DBC2 losses has been detected in various carcinomas including prostate, breast, lung, colon, rectum, bladder, liver and larynx carcinoma (Emi et al, 1992;Lundgren et al, 1992;Bova et al, 1993;Fujiwara et al, 1993;Sunwoo et al, 1996).…”