Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Proc Natl Acad Sci U S A
2004 Dec 28;10152:18123-8. doi: 10.1073/pnas.0408273101.
Show Gene links
Show Anatomy links
Estrogen mediates Aurora-A overexpression, centrosome amplification, chromosomal instability, and breast cancer in female ACI rats.
Li JJ
,
Weroha SJ
,
Lingle WL
,
Papa D
,
Salisbury JL
,
Li SA
.
???displayArticle.abstract???
Estrogens play a crucial role in the causation and development of sporadic human breast cancer (BC). Chromosomal instability (CIN) is a defining trait of early human ductal carcinoma in situ (DCIS) and is believed to precipitate breast oncogenesis. We reported earlier that 100% of female ACI (August/Copenhagen/Irish) rats treated with essentially physiological serum levels of 17beta-estradiol lead to mammary gland tumors with histopathologic, cellular, molecular, and ploidy changes remarkably similar to those seen in human DCIS and invasive sporadic ductal BC. Aurora-A (Aur-A), a centrosome kinase, and centrosome amplification have been implicated in the origin of aneuploidy via CIN. After 4 mo of estradiol treatment, levels of Aur-A and centrosomal proteins, gamma-tubulin and centrin, rose significantly in female ACI rat mammary glands and remained elevated in mammary tumors at 5-6 mo of estrogen treatment. Centrosome amplification was initially detected at 3 mo of treatment in focal dysplasias, before DCIS. At 5-6 mo, 90% of the mammary tumor centrosomes were amplified. Comparative genomic hybridization revealed nonrandom amplified chromosome regions in seven chromosomes with a frequency of 55-82% in 11 primary tumors each from individual rats. Thus, we report that estrogen is causally linked via estrogen receptor alpha to Aur-A overexpression, centrosome amplification, CIN, and aneuploidy leading to BC in susceptible mammary gland cells.
Adami,
The aetiology and pathogenesis of human breast cancer.
1995, Pubmed
Adami,
The aetiology and pathogenesis of human breast cancer.
1995,
Pubmed
Aldaz,
Chromosome alterations in rat mammary tumor progression.
1992,
Pubmed
Arnerlöv,
Intratumoral variations in DNA ploidy and s-phase fraction in human breast cancer.
2001,
Pubmed
Blankenstein,
The effect of subcutaneous administration of oestrogens on plasma oestrogen levels and tumour incidence in female rats.
1977,
Pubmed
Brinkley,
Supernumerary centrosomes and cancer: Boveri's hypothesis resurrected.
1998,
Pubmed
Carmena,
The cellular geography of aurora kinases.
2003,
Pubmed
,
Xenbase
Carroll,
Centrosome hyperamplification in human cancer: chromosome instability induced by p53 mutation and/or Mdm2 overexpression.
1999,
Pubmed
Chetrite,
Comparison of estrogen concentrations, estrone sulfatase and aromatase activities in normal, and in cancerous, human breast tissues.
2000,
Pubmed
Clemons,
Estrogen and the risk of breast cancer.
2001,
Pubmed
Colditz,
Prospective study of estrogen replacement therapy and risk of breast cancer in postmenopausal women.
1990,
Pubmed
D'Assoro,
Centrosome amplification and the development of cancer.
2002,
Pubmed
Daling,
Relation of regimens of combined hormone replacement therapy to lobular, ductal, and other histologic types of breast carcinoma.
2002,
Pubmed
Deming,
C-myc amplification in breast cancer: a meta-analysis of its occurrence and prognostic relevance.
2000,
Pubmed
Dutertre,
On the role of aurora-A in centrosome function.
2002,
Pubmed
Errabolu,
Cloning of a cDNA encoding human centrin, an EF-hand protein of centrosomes and mitotic spindle poles.
1994,
Pubmed
,
Xenbase
Feigelson,
Estrogens and breast cancer.
1996,
Pubmed
Felsher,
Transient excess of MYC activity can elicit genomic instability and tumorigenesis.
1999,
Pubmed
Fry,
The Nek2 protein kinase: a novel regulator of centrosome structure.
2002,
Pubmed
,
Xenbase
Gemmell,
An efficient method for the extraction of DNA from vertebrate tissues.
1996,
Pubmed
Goepfert,
Centrosome amplification and overexpression of aurora A are early events in rat mammary carcinogenesis.
2002,
Pubmed
,
Xenbase
Haag,
Allelic imbalance in mammary carcinomas induced by either 7,12-dimethylbenz[a]anthracene or ionizing radiation in rats carrying genes conferring differential susceptibilities to mammary carcinogenesis.
1996,
Pubmed
Hoque,
Loss of aurora A/STK15/BTAK overexpression correlates with transition of in situ to invasive ductal carcinoma of the breast.
2003,
Pubmed
Hynes,
Myc and mammary cancer: Myc is a downstream effector of the ErbB2 receptor tyrosine kinase.
2001,
Pubmed
Kallioniemi,
Optimizing comparative genomic hybridization for analysis of DNA sequence copy number changes in solid tumors.
1994,
Pubmed
Katayama,
The Aurora kinases: role in cell transformation and tumorigenesis.
2003,
Pubmed
,
Xenbase
King,
Inherited breast and ovarian cancer. What are the risks? What are the choices?
1993,
Pubmed
Krämer,
Centrosome replication, genomic instability and cancer.
2002,
Pubmed
Lajoie-Mazenc,
A single gamma-tubulin gene and mRNA, but two gamma-tubulin polypeptides differing by their binding to the spindle pole organizing centres.
1996,
Pubmed
Leal,
Ductal carcinoma in situ of the breast. Histologic categorization and its relationship to ploidy and immunohistochemical expression of hormone receptors, p53, and c-erbB-2 protein.
1995,
Pubmed
Li,
Overexpression and amplification of c-myc in the Syrian hamster kidney during estrogen carcinogenesis: a probable critical role in neoplastic transformation.
1999,
Pubmed
Li,
Hormone replacement therapy in relation to risk of lobular and ductal breast carcinoma in middle-aged women.
2000,
Pubmed
Li,
ER and PR in renomedullary interstitial cells during Syrian hamster estrogen-induced tumorigenesis: evidence for receptor-mediated oncogenesis.
2001,
Pubmed
Li,
Ploidy differences between hormone- and chemical carcinogen-induced rat mammary neoplasms: comparison to invasive human ductal breast cancer.
2002,
Pubmed
Li,
Prevention of solely estrogen-induced mammary tumors in female aci rats by tamoxifen: evidence for estrogen receptor mediation.
2002,
Pubmed
Li,
c-Myc overexpression uncouples DNA replication from mitosis.
1999,
Pubmed
Li,
Aneuploidy vs. gene mutation hypothesis of cancer: recent study claims mutation but is found to support aneuploidy.
2000,
Pubmed
Liao,
Unusual deregulation of cell cycle components in early and frank estrogen-induced renal neoplasias in the Syrian hamster.
2000,
Pubmed
Lingle,
Centrosome amplification drives chromosomal instability in breast tumor development.
2002,
Pubmed
Mai,
Genomic instability in MycER-activated Rat1A-MycER cells.
1996,
Pubmed
Makris,
Cytological evaluation of biological prognostic markers from primary breast carcinomas.
1997,
Pubmed
Miyoshi,
Association of centrosomal kinase STK15/BTAK mRNA expression with chromosomal instability in human breast cancers.
2001,
Pubmed
Mohapatra,
Detection of multiple gains and losses of genetic material in ten glioma cell lines by comparative genomic hybridization.
1995,
Pubmed
Nigg,
Mitotic kinases as regulators of cell division and its checkpoints.
2001,
Pubmed
Oakley,
Identification of gamma-tubulin, a new member of the tubulin superfamily encoded by mipA gene of Aspergillus nidulans.
1989,
Pubmed
Papa,
Comparative genomic hybridization of estrogen-induced ectopic uterine-like stem cell neoplasms in the hamster kidney: nonrandom chromosomal alterations.
2003,
Pubmed
Pihan,
Centrosome abnormalities and chromosome instability occur together in pre-invasive carcinomas.
2003,
Pubmed
Salisbury,
The contribution of epigenetic changes to abnormal centrosomes and genomic instability in breast cancer.
2001,
Pubmed
Salisbury,
Centrosomes and cancer.
1999,
Pubmed
Smith,
Malignant transformation of mammalian cells initiated by constitutive expression of the polo-like kinase.
1997,
Pubmed
Spruck,
Deregulated cyclin E induces chromosome instability.
1999,
Pubmed
Starita,
BRCA1-dependent ubiquitination of gamma-tubulin regulates centrosome number.
2004,
Pubmed
Tanaka,
Centrosomal kinase AIK1 is overexpressed in invasive ductal carcinoma of the breast.
1999,
Pubmed
Thijssen,
Uptake and concentration of steroid hormones in mammary tissues.
1986,
Pubmed
Vermeulen,
Aromatase, 17 beta-hydroxysteroid dehydrogenase and intratissular sex hormone concentrations in cancerous and normal glandular breast tissue in postmenopausal women.
1986,
Pubmed
Warner,
Targeting Aurora-2 kinase in cancer.
2003,
Pubmed
Zhou,
Tumour amplified kinase STK15/BTAK induces centrosome amplification, aneuploidy and transformation.
1998,
Pubmed
