Over‐expression of heat shock proteins in carcinogenic endometrium

We have previously shown that the subcellular localization of β‐catenin changes according to the cell proliferation status of the human endometrium, suggesting a role of intercellular transduction in cell growth control in human endometrium not only in the physiological but also in the carcinogenic condition. To further study the possible role of heat shock proteins (HSPs) in growth control, we immunohistochemically analyzed 92 endometrial samples, 30 of normal endometrium, 20 of endometrial hyperplasia and 42 of endometrial cancer, for expression of HSP27, HSP70, HSP90, estrogen receptor (ER) and progesterone receptor. HSP27 and HSP90 were detected in endometrial epithelium strongly in the proliferative phase and weakly in the secretory phase during the menstrual cycle according to the serum estradiol level. However, they were over‐expressed in endometrial hyperplasia, especially HSP27. In endometrial cancer, HSP27 expression was heterogenic among the glands and lower than that in the proliferative phase and endometrial hyperplasia. HSP27 over‐expression was also observed in samples including endometrial cancer and associated hyperplasia. Results of Western blotting followed those of immunohistochemistry. HSP70 was not changed during the menstrual cycle, as HSP27 and HSP90 were, and was rather stably expressed in endometrial hyperplasia and cancer. Our results suggest that HSP27 and HSP90 contribute to cell proliferation in endometrial epithelium and that over‐expression of HSP27 in endometrial hyperplasia occurs as a result of the activated condition of ER, though in cancer it decreases according to the loss of function of ER. © 2001 Wiley‐Liss, Inc.

[1]  Tsuyoshi Saito,et al.  Nuclear localization of β‐catenin in normal and carcinogenic endometrium , 1999, Molecular carcinogenesis.

[2]  J. P. Geisler,et al.  A study of heat shock protein 27 in endometrial carcinoma. , 1999, Gynecologic oncology.

[3]  E. Solary,et al.  Heat shock protein 27 enhances the tumorigenicity of immunogenic rat colon carcinoma cell clones. , 1998, Cancer research.

[4]  Tsuyoshi Saito,et al.  Induction of cell transformation by mutated 16K vacuolar H+-atpase (ductin) is accompanied by down-regulation of gap junctional intercellular communication and translocation of connexin 43 in NIH3T3 cells , 1998, Oncogene.

[5]  N. Martel,et al.  Proliferation-associated regulation of telomerase activity in human endometrium and its potential implication in early cancer diagnosis. , 1997, Biochemical and biophysical research communications.

[6]  S. Safe,et al.  Role of estrogen receptor/Sp1 complexes in estrogen-induced heat shock protein 27 gene expression. , 1996, Molecular endocrinology.

[7]  L. Weber,et al.  Effect of overexpression of the small heat shock protein HSP27 on the heat and drug sensitivities of human testis tumor cells. , 1996, Cancer research.

[8]  I. Konishi,et al.  Expression of heat shock proteins HSP70 and HSP90 in endometrial carcinomas: Correlation with clinicopathology, sex steroid receptor status, and p53 protein expression , 1996, Cancer.

[9]  P. Tang,et al.  Evidence for oestrogenic regulation of heat shock protein expression in human endometrium and steroid-responsive cell lines. , 1995, European journal of endocrinology.

[10]  I. Konishi,et al.  Immunohistochemical localization of heat shock proteins HSP70 and HSP90 in the human endometrium: correlation with sex steroid receptors and Ki-67 antigen expression. , 1995, The Journal of clinical endocrinology and metabolism.

[11]  K. Korach,et al.  Heat shock protein 90 strongly stimulates the binding of purified estrogen receptor to its responsive element. , 1994, Journal of biochemistry.

[12]  K. Hancock,et al.  Expression of heat shock protein 70 kDa in human endometrium of normal and infertile women. , 1994, Human reproduction.

[13]  M. Whitehead,et al.  Hormonal regulation of HSP27 expression in human endometrial epithelial and stromal cells , 1994, Molecular and Cellular Endocrinology.

[14]  W. McGuire,et al.  Biological and clinical implications of heat shock protein 27,000 (Hsp27): a review. , 1993, Journal of the National Cancer Institute.

[15]  M. Gaestel,et al.  Small heat shock proteins are molecular chaperones. , 1993, The Journal of biological chemistry.

[16]  B. O’Malley,et al.  Characterization of progesterone receptor binding to the 90- and 70-kDa heat shock proteins. , 1991, The Journal of biological chemistry.

[17]  B. O’Malley,et al.  Progesterone enhances target gene transcription by receptor free of heat shock proteins hsp90, hsp56, and hsp70 , 1991, Molecular and cellular biology.

[18]  P. Pechan Heat shock proteins and cell proliferation , 1991, FEBS letters.

[19]  A. Ferenczy,et al.  Immunocytochemical study of progesterone receptors in hyperplastic and neoplastic endometrial tissues. , 1988, Cancer research.

[20]  G. Greene,et al.  Immunohistochemical analysis of human uterine estrogen and progesterone receptors throughout the menstrual cycle. , 1988, The Journal of clinical endocrinology and metabolism.

[21]  R. King,et al.  Immunoradiometric studies with monoclonal antibody against a component related to human estrogen receptor. , 1985, Cancer research.

[22]  W. McGuire,et al.  Quantitative enzyme-linked immunosorbent assay for the estrogen-regulated Mr 24,000 protein in human breast tumors: correlation with estrogen and progesterone receptors. , 1985, Cancer research.

[23]  D. Edwards,et al.  Estrogen induced synthesis of specific proteins in human breast cancer cells. , 1980, Biochemical and biophysical research communications.

[24]  R. Noyes,et al.  Dating the endometrial biopsy. , 1950, American journal of obstetrics and gynecology.

[25]  S. Tabibzadeh,et al.  Heat shock proteins in human endometrium throughout the menstrual cycle. , 1999, Infectious diseases in obstetrics and gynecology.

[26]  D. Edwards,et al.  The presence of an estrogen-regulated protein detected by monoclonal antibody in abnormal human endometrium. , 1985, The Journal of clinical endocrinology and metabolism.