title: Cyclin E deregulation is an early event in the development of breast cancer.
abstract: Cyclin E has been shown to be overexpressed in some human breast cancers, however, data to support deregulation of cyclin E as an early event in human mammary tumor development is lacking. We analyzed surgical specimens from 183 patients with breast carcinomas and evaluated cyclin E expression in areas of invasive carcinoma, adjacent carcinoma in situ (CIS), and non-neoplastic breast parenchyma. Overexpression of cyclin E was seen in one-third of invasive carcinoma samples, one-third of the CIS component and nearly half of the non-neoplastic breast epithelial cells adjacent to carcinoma (44% vs. 33%, P < or = 0.05). Nuclear labeling for cyclin E was highly concordant between areas of in invasive carcinoma, CIS and non-neoplastic breast epithelial cells from the same patient (P < 0.0001). Localization of cyclin E to the cytoplasm was seen in a small proportion of tumor samples. Our findings suggest that cyclin E deregulation is an early event in the progression from histologically benign mammary epithelial cells to invasive carcinoma and occurs through both overexpression and altered cellular localization.
authors.affiliation: Department of Pathology, University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Shaye
authors.forename: Aysegul
authors.initials: A
authors.lastname: Sahin
authors.forename: Qiang
authors.initials: Q
authors.lastname: Hao
authors.forename: Kelly
authors.initials: K
authors.lastname: Hunt
authors.forename: Khandan
authors.initials: K
authors.lastname: Keyomarsi
authors.forename: Isabelle
authors.initials: I
authors.lastname: Bedrosian
mesh_terms: D015153:Blotting, Western; D001940:Breast / Q000378:metabolism* / Q000473:pathology; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002278:Carcinoma in Situ / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism; D019927:Cyclin E / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D009361:Neoplasm Invasiveness; D015513:Oncogene Proteins / Q000378:metabolism*; D011230:Precancerous Conditions / Q000378:metabolism* / Q000473:pathology; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D019927:Cyclin E; D015513:Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C475820:CCNE1 protein, human