Cell proliferation and apoptosis in human uterine leiomyomas and myometria.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Dixon, D; Flake, GP; Moore, AB; He, H; Haseman, JK; Risinger, JI; Lancaster, JM; Berchuck, A; Barrett, JC; Robboy, SJ

Published Date

  • July 2002

Published In

Volume / Issue

  • 441 / 1

Start / End Page

  • 53 - 62

PubMed ID

  • 12111201

Pubmed Central ID

  • 12111201

Electronic International Standard Serial Number (EISSN)

  • 1432-2307

International Standard Serial Number (ISSN)

  • 0945-6317

Digital Object Identifier (DOI)

  • 10.1007/s00428-001-0568-7

Language

  • eng