Growth Retardation and Tumour Inhibition by BRCA1

Holt, Jeffrey T.; Thompson, Marilyn E.; Szabo, Csilla I.; Robinson-Benion, Cheryl; Arteaga, Carlos L.; King, Mary‐Claire; Jensen, Roy A.

doi:10.1097/00006254-199607000-00014

Cited by 70 publications

(97 citation statements)

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“…Virally mediated over-expression of BRCA1 abolished the proliferation of breast and ovarian cancer cells, while anti-sense knockdown caused increased proliferation (Thompson et al, 1995;Holt et al, 1996). In our experience, the expression of wtBRCA1 using a CMV promoter-driven expression plasmid caused a modest reduction of in vitro proliferation, but a marked reduction of the growth of wtBRCA1 cell clones as subcutaneous tumors in nude mice (Fan et al, 1998b(Fan et al, , 2001b.…”

Section: Functional Activities Of Brca1 Cell Cycle Regulation and Gromentioning

confidence: 81%

“…These findings suggest that the TAD of BRCA1 is required for suppression of breast but not ovarian cancer growth. On the other hand, antisense inhibition of BRCA1 enhanced the in vitro proliferation of MCF-7 and normal mammary epithelial cells, but not other epithelial cell types (Holt et al, 1996).…”

Section: Functional Activities Of Brca1 Cell Cycle Regulation and Gromentioning

confidence: 88%

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BRCA1 gene in breast cancer

Rosen

Fan

Pestell

et al. 2003

Journal Cellular Physiology

237

195

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The BRCA1 gene was identified and cloned in 1994 based on its linkage to early onset breast cancer and breast-ovarian cancer syndromes in women. While inherited mutations of BRCA1 are responsible for about 40-45% of hereditary breast cancers, these mutations account for only 2-3% of all breast cancers, since the BRCA1 gene is rarely mutated in sporadic breast cancers. However, BRCA1 expression is frequently reduced or absent in sporadic cancers, suggesting a much wider role in mammary carcinogenesis. Since BRCA1 was cloned in 1994, its molecular function has been the subject of intense investigation. These studies have revealed multiple functions of the BRCA1 that may contribute to its tumor suppressor activity, including roles in: cell cycle progression, several highly specialized DNA repair processes, DNA damage-responsive cell cycle checkpoints, regulation of a set of specific transcriptional pathways, and apoptosis. Many of these functions are linked to protein:protein interactions involving different portions of the 1,863 amino acid (aa) BRCA1 protein. BRCA1 functions in cell cycle progression and the DNA damage response appear to be regulated by distinct and specific phosphorylation events, but the molecular pathways activated by these phosphorylations are only beginning to be unraveled. In addition, the reason that BRCA1 mutation carriers develop specific tumor types (breast and ovarian cancers in women and possibly prostate cancers in men) is not clearly understood. Elucidation of the precise molecular functions of the BRCA1 gene product will greatly enhance our understanding of the pathogenesis of hereditary as well as sporadic mammary carcinogenesis.

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Section: Functional Activities Of Brca1 Cell Cycle Regulation and Gromentioning

confidence: 81%

Section: Functional Activities Of Brca1 Cell Cycle Regulation and Gromentioning

confidence: 88%

BRCA1 gene in breast cancer

Rosen

Fan

Pestell

et al. 2003

Journal Cellular Physiology

237

195

View full text Add to dashboard Cite

show abstract

“…Also downregulated significantly were a few known tumor suppressor genes, such as RB1 (regulating cell cycling for preventing cancer development) 25,26 and BRCA1 (preserving chromosomal structure and suppressing genomic instability). 27,28 Among these suppressor genes, mutation of BRCA1 is already known to be one of the predisposing factors to ovarian cancer. 27 Downregulation of a couple of genes requires further brief discussion.…”

Section: Discussionmentioning

confidence: 99%

“…27,28 Among these suppressor genes, mutation of BRCA1 is already known to be one of the predisposing factors to ovarian cancer. 27 Downregulation of a couple of genes requires further brief discussion. First, FSH treatment in this experiment reduced BS69 transcript expression 14.9 times lower than the control level.…”

Section: Discussionmentioning

confidence: 99%

Follicle stimulating hormone‐induced growth promotion and gene expression profiles on ovarian surface epithelial cells

Liu

Chen

et al. 2004

Intl Journal of Cancer

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Ovarian cancer (OC) is one of the leading causes of death in patients with gynecologic malignancies. The vast majority of ovarian cancers have a cell origin of ovarian surface epithelium (OSE), which is derived from Mullerian epithelium covering embryonic gonads. Since the incidence of OC sharply increases after menopause, critical roles of gonadotropins and their receptors in ovarian carcinogenesis are speculated by investigators. 1 Follicle stimulating hormone (FSH), through interaction with its specific receptor, FSHR, plays an essential role in mammalian reproduction and ovarian folliculogenesis. 2 Binding of FSH to FSHR results in adenylyl cyclase activation leading to cAMP synthesis, associated with intracellular rise of Ca 2ϩ , activation of protein kinase A (PKA) and other downstream signal transduction pathways. [2][3][4][5][6] It has been reported that FSH treatment stimulates cell proliferation on normal human OSE cells, immortalized OSE cells and OC cell lines. 7,8 However, little has been known on the effects of FSH in the process of tumorigenesis and growth stimulation on human OSE at molecular levels.In this study, we first determined FSHR expression levels quantitatively in human ovarian normal and neoplastic tissues. Then the effects of FSH treatment on cell proliferation were examined using human OSE cell lines as well as Chinese hamster ovary (CHO) cell lines permanently transfected with human FSHR. Finally, gene expression profiles for FSH treatment were analyzed by cDNA MicroArray using a selected human OSE cell line that has best growth response to FSH treatment from cell proliferation assays. MATERIAL AND METHODS

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“…Gown, in prep.) tumors from patients not selected for family history; accelerated growth of normal and malignant mammary epithelial cells upon experimental inhibition of BRCA1 expression with antisense oligonucleotides (Thompson et al 1995); and inhibition of malignant breast and ovarian cancer cell growth in culture as well as suppression of MCF7 breast cancer cell tumorigenesis in mice by overexpression of wild-type BRCA1 (Holt et al 1996).…”

mentioning

confidence: 99%

Complete genomic sequence and analysis of 117 kb of human DNA containing the gene BRCA1.

Smith¹,

Lee²,

Szabo³

et al. 1996

Genome Res.

252

189

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Over 100 distinct disease-associated mutations have been identified in the breast-ovarian cancer susceptibility gene BRCAI. Loss of the wild-type allele in >90% of tumors from patients with inherited BRCAI mutations indicates tumor suppressive function. The low incidence of somatic mutations suggests that BRCAI inactivation in sporadic tumors occurs by alternative mechanisms, such as interstitial chromosomal deletion or reduced transcription. To identify possible features of the BRCA1 genomic region that may contribute to chromosomal instability as well as potential transcriptional regulatory elements, a 117,143-bp DNA sequence encompassing BRCA1 was obtained by random sequencing of four cosmids identified from a human chromosome 17 specific library. The 24 exons of BRCAI span an 81-kb region that has an unusually high density of AJu repetitive DNA {41.5%), but relatively low density [4.8%) of other repetitive sequences. BRCAI intron lengths range in size from 403 bp to 9.2 kb and contain the intragenic microsatellite markers DI7S1323, DI7SI322, and DI7S855, which localize to introns 12, 19, and 20, respectively. In addition to BRCAI, the contig contains two complete genes: RhoT, a member of the rho family of GTP binding proteins, and VAT1, an abundant membrane protein of cholinergic synaptic vesicles. Partial sequences of the IAI-JB B-box protein pseudogene and lip JS, an interferon induced leucine zipper protein, reside within the contig. An L21 ribosomal protein pseudogene is embedded in BRCA1 intron 13. The order of genes on the chromosome is: centromere-lFP JS-VATI-P, hoT-BRCAI-IAI-JB-telomere.[The sequence data described in this paper have been submitted to GenBank under accession no. L78833.] Inherited mutations in the breast-ovarian cancer susceptibility gene, BRCA1 (Hall et al. 1990;Miki et al. 1994), confer a lifetime risk of breast cancer greater than 80% and an increased risk of ovarian cancer (Newman et al. 1988;Easton et al. 1993;Ford et al. 1994). Evidence for tumor suppressive function of BRCA1 derives from the high proportion (87%) of truncating germ-line mutations, which likely represent loss-of-function alterations (Castilla et

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Growth Retardation and Tumour Inhibition by BRCA1

Cited by 70 publications

References 0 publications

BRCA1 gene in breast cancer

BRCA1 gene in breast cancer

Follicle stimulating hormone‐induced growth promotion and gene expression profiles on ovarian surface epithelial cells

Complete genomic sequence and analysis of 117 kb of human DNA containing the gene BRCA1.

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