PMID- 15987425 OWN - NLM STAT- MEDLINE DCOM- 20060125 LR - 20220316 IS - 1465-542X (Electronic) IS - 1465-5411 (Print) IS - 1465-5411 (Linking) VI - 7 IP - 3 DP - 2005 TI - Assessment of the proliferative, apoptotic and cellular renovation indices of the human mammary epithelium during the follicular and luteal phases of the menstrual cycle. PG - R306-13 AB - INTRODUCTION: During the menstrual cycle, the mammary gland goes through sequential waves of proliferation and apoptosis. In mammary epithelial cells, hormonal and non-hormonal factors regulate apoptosis. To determine the cyclical effects of gonadal steroids on breast homeostasis, we evaluated the apoptotic index (AI) determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining in human mammary epithelial cells during the spontaneous menstrual cycle and correlated it with cellular proliferation as determined by the expression of Ki-67 during the same period. METHODS: Normal breast tissue samples were obtained from 42 randomly selected patients in the proliferative (n = 21) and luteal (n = 21) phases. Menstrual cycle phase characterization was based on the date of the last and subsequent menses, and on progesterone serum levels obtained at the time of biopsy. RESULTS: The proliferation index (PI), defined as the number of Ki-67-positive nuclei per 1,000 epithelial cells, was significantly larger in the luteal phase (30.46) than in the follicular phase (13.45; P = 0.0033). The AI was defined as the number of TUNEL-positive cells per 1,000 epithelial cells. The average AI values in both phases of the menstrual cycle were not statistically significant (P = 0.21). However, the cell renewal index (CRI = PI/AI) was significantly higher in the luteal phase (P = 0.033). A significant cyclical variation of PI, AI and CRI was observed. PI and AI peaks occurred on about the 24th day of the menstrual cycle, whereas the CRI reached higher values on the 28th day. CONCLUSIONS: We conclude that proliferative activity is dependent mainly on hormonal fluctuations, whereas apoptotic activity is probably regulated by hormonal and non-hormonal factors. FAU - Navarrete, Maria Alicia H AU - Navarrete MA AD - Department of Gyneology, Mastology Division, Federal University of Sao Paulo, Sao Paulo, Brazil. chile@stanford.edu FAU - Maier, Carolina M AU - Maier CM FAU - Falzoni, Roberto AU - Falzoni R FAU - Quadros, Luiz Gerk de Azevedo AU - Quadros LG FAU - Lima, Geraldo R AU - Lima GR FAU - Baracat, Edmund C AU - Baracat EC FAU - Nazario, Afonso C P AU - Nazario AC LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20050216 PL - England TA - Breast Cancer Res JT - Breast cancer research : BCR JID - 100927353 RN - 0 (Ki-67 Antigen) RN - 4G7DS2Q64Y (Progesterone) SB - IM MH - Adolescent MH - Adult MH - *Apoptosis MH - *Cell Proliferation MH - Female MH - Follicular Phase/*physiology MH - Homeostasis MH - Humans MH - In Situ Nick-End Labeling MH - Ki-67 Antigen/analysis MH - Kinetics MH - Luteal Phase/*physiology MH - Mammary Glands, Human/*cytology/physiology MH - Progesterone/blood/physiology PMC - PMC1143573 EDAT- 2005/07/01 09:00 MHDA- 2006/01/26 09:00 PMCR- 2005/02/16 CRDT- 2005/07/01 09:00 PHST- 2004/06/06 00:00 [received] PHST- 2004/10/08 00:00 [revised] PHST- 2004/12/20 00:00 [accepted] PHST- 2005/07/01 09:00 [pubmed] PHST- 2006/01/26 09:00 [medline] PHST- 2005/07/01 09:00 [entrez] PHST- 2005/02/16 00:00 [pmc-release] AID - bcr994 [pii] AID - 10.1186/bcr994 [doi] PST - ppublish SO - Breast Cancer Res. 2005;7(3):R306-13. doi: 10.1186/bcr994. Epub 2005 Feb 16.