Chronic Stress Induces the Expression of the Proliferation Marker Ki-67 in Female Rat Breast, NAGWA E. EL-NEFIAWY, AHMED DESOUKY, SAMY A. ABUSIKKIEN and HESHAM I. ABDALLAH
Abstract
Background: It is thought that the dynamic ability of breast cells to be continuously influenced and remodeled under the influence of hormones and growth factors makes them susceptible to carcinogenesis. Few studies investigated the effect of estrous cycle hormones on mammary gland proliferation. However, the relationship between stress and mammary gland proliferation remains to be elucidated.
Aim of the Work: To define the impact of stress exposure (acute and chronic) on proliferation, apoptosis and steroid receptor expression in adult female rat breast.
Material and Methods: Vaginal smears were performed first to define rats at same phase of estrous cycle. 18 Adult female albino rats were divided into three equal groups; control, acute stress, and chronic stress groups. Rats were subjected to restraint stress for either 5h once (acute stress) or 5h daily for 2 weeks in chronic stress. At the end of experiment fixed pairs of breast were collected, fixed in 10% formalin and processed into paraffin blocks. Cut sections were stained with H & E and immunohistochemically stained for steroid receptors estrogen (ER) and progesterone (PR), pro-liferation marker (Ki-67), and P53 antibody.
Results: Histologically evident proliferation of the epi-thelial compartment was detected in chronic stress group. Acute stress group revealed massive inflammatory criteria like blood congestion and cell infiltrates in breast parenchyma. Immunohistochemistry showed negative immune staining for ER and trivial positive immune staining for PR with stromal localization in the three groups. Proliferation marker (Ki-67) as well as P53 revealed marked intense immune staining in chronic stress group contrary to other groups.
Conclusion: Chronic but not acute stress induces prolif-eration of breast parenchyma regardless of steroid receptors expression as shown by the expression of Ki-67 and P53 markers. The novel observations presented here might have implications for understanding breast biology together with the pathogenesis of breast cancer.