Cell proliferation and apoptosis in human uterine leiomyomas and myometria

Abstract

To determine the role of cell proliferation and apoptosis in uterine leiomyoma growth, we studied protein expression of two major regulatory proteins of apoptosis -- Bcl-2 (anti-apoptotic) and Bax (pro-apoptotic) -- and two endogenous markers of cell replication - proliferating cell nuclear antigen (PCNA) and Ki-67 - in tumors and matched myometrium from premenopausal women. Conventional mitotic indices also were determined, and all proliferation data were correlated to tumor size. In situ end-labeling of fragmented DNA and routine histology were used to assess apoptosis. Our results showed that the apoptosis-regulating proteins (Bcl-2 and Bax) were expressed in the cytoplasm of the leiomyoma and myometrial smooth muscle cells throughout the menstrual cycle. Bax expression differed from Bcl-2 in that it also was found in the cytoplasm of vascular smooth muscle cells of the myometria and tumors. Both tumors and myometrial samples expressed 26-kDa and 21-kDa proteins that reacted with antibodies directed towards Bcl-2 and Bax, respectively. Apoptosis was not a prominent feature of uterine leiomyomas or myometrium. PCNA- and Ki-67-labeling and mitotic counts were significantly ( P<0.05) higher in leiomyomas than in matched myometrial samples. Proliferative activity was variable for individual tumors of the same patient and independent of tumor size. Our results suggest that altered apoptosis by overexpression of Bcl-2 or by decreased expression of Bax does not appear to be a major factor in uterine leiomyoma growth. We conclude that increased cell proliferation is the most significant contributor to growth and that the proliferative state is autonomous for each tumor in a given patient and is independent of tumor size.

Therapeutic mechanism of ginkgo biloba exocarp polysaccharides on gastric cancer

“…Bcl-2 was an important apoptosis-inhibitory gene [18][19][20] , it included a nucleus molecule that can block cell apoptosis, prolong cell lives, accelerate DNA repairing, and thus promoting tumor genesis and development. So it could down-regulate cell apoptosis [21][22][23][24][25] . This clinical study and examination of cellular ultrastructures showed clues of apoptosis induced by GBEP in human gastric cancer cells.…”

Uterine fibroids in menopause women: the effect of hormone therapy

“…Объем доминантного миоматозного узла существенно не менялся. Полу-ченные нами результаты согласуются с данными других авторов [8,9].…”

“…Согласно данным других источников литературы [5,8,10], на фоне проведения МГТ стандартными дозами имеется риск роста миоматозных узлов, что ограничивает применение данной терапии у боль-ных с миомой матки.…”

Optimized Culture Conditions for Tissue Explants of Uterine Leiomyoma

“…However, it must be kept in mind that this also includes exploring the current problem of the immense heterogeneity of this tissue. Even myoma from the same patient can have very different proliferation rates, apparently independent of the tumour size [3]. This makes optimisation of culture conditions for these tissues extremely difficult.…”

“…The lifelong risk of getting myomas is about 70%, and 10 to 25% of patients have symptoms such as pain, infertility, or bleeding problems, which seem to correlate with size, quantity and locations of the tumours [1]. Myomas are hormone dependant, but there are also other modulators of genesis and growth such as different tumour suppressors [2], locale cytokines and growth factors [3,4], and, in addition, macrophages, T-cells, and mastocytes were found to be increased in myomas [5]. Cell form and cytoskeleton are modified as well as amount, structure, and compounds of the extracellular matrix [6,7].…”