title: Correlation between the expression of apoptosis-related bcl-2 and p53 oncoproteins and the carcinogenesis and progression of breast carcinomas.
abstract: The proto-oncogene bcl-2, which is implicated in the regulation of cell death by inhibiting apoptosis, is reported to be expressed in breast tissues. The wild-type p53 has been shown to induce apoptosis, which can be inhibited by bcl-2 expression. However, the role of bcl-2 and p53 expression in breast carcinogenesis has not been clarified. The purpose of this study was to evaluate bcl-2 and p53 expression in normal breast epithelia cells, as well as in intraductal and invasive cancerous lesions of breast cancer tissue using an immunohistochemical method and to clarify their role in the development of breast cancer. The nuclear accumulation of p53 was also evaluated by quantitative image analysis. Expression of bcl-2 was found in 79 of 82 (96%) normal ductal epithelial cells, in 50 of 63 (79%) intraductal carcinomas, and in 62 of 137 (45%) invasive carcinomas, respectively. Higher bcl-2 expression was observed in normal epithelial cells than in intraductal and invasive cancerous cells (P < 0.0001). Furthermore, bcl-2 positivity in intraductal lesions was significantly higher than in invasive cancerous lesions (P < 0.05). No p53 nuclear accumulation was observed in normal breast epithelial cells. Fifteen of 63 (23.8%) intraductal cancerous lesions and 41 of 137 (30%) invasive cancerous lesions were positive for p53 expression. An inverse relationship was shown between bcl-2 and p53 expression in invasive carcinomas. We demonstrated that bcl-2 expression exists in most of normal ductal epithelial cells and gradually decreases during the development of breast cancer, i.e. , from a normal epithelium to intraductal carcinoma, and from intraductal to invasive carcinoma, and that p53 expression may occur early in breast cancer development and increases during progression.
authors.affiliation: Department of Surgery II, Fukushima Medical College, 1 Hikarigaoka, Fukushima 960-12, Japan. zhang@cc.fmu.ac.jp
authors.forename: G J
authors.initials: GJ
authors.lastname: Zhang
authors.forename: I
authors.initials: I
authors.lastname: Kimijima
authors.forename: R
authors.initials: R
authors.lastname: Abe
authors.forename: M
authors.initials: M
authors.lastname: Kanno
authors.forename: N
authors.initials: N
authors.lastname: Katagata
authors.forename: K
authors.initials: K
authors.lastname: Hara
authors.forename: T
authors.initials: T
authors.lastname: Watanabe
authors.forename: A
authors.initials: A
authors.lastname: Tsuchiya
mesh_terms: D017209:Apoptosis; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics / Q000473:pathology / Q000601:surgery; D002467:Cell Nucleus / Q000473:pathology; D004847:Epithelial Cells / Q000166:cytology / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D019254:Genes, bcl-2; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D009361:Neoplasm Invasiveness; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis*; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53