Characterization of Mullerian inhibiting substance binding on cervical carcinoma cells demonstrated by immunocytochemistry

Wang, Jaang-Jiun; Roffler, Steve R.; Chou, Hsiu-Hui; Yin, Fon-Yi; Yin, Chang‐Sheng

doi:10.1016/0040-8166(94)90030-2

Cited by 5 publications

(8 citation statements)

References 19 publications

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“…In support of the idea that cervical cancer cells might be a target for MIS, Wang et al (19,20) demonstrated by electron microscopy that several cervical cancer cell lines (CaSki and HeLa) bind and internalize gold-labeled MIS ligand purified from avian testes. In addition, the spectrum of cell cycle defects in these cell lines is similar to that observed in OVCAR8 cells, which are sensitive to MIS (6).…”

Section: Ullerian Inhibiting Substance (Mis) Also Known As Anti-mentioning

confidence: 99%

“…Although cervical cancer cells bind MIS (19,20), receptor expression has not been formally demonstrated, and the functional consequences of this interaction remain unknown. Therefore, we examined effects of MIS on cell cycle regulatory proteins, comparing findings in cervical cancer cells to those previously reported for ovarian cancer cells (6).…”

Section: Ullerian Inhibiting Substance (Mis) Also Known As Anti-mentioning

confidence: 99%

“…Mullerianderived cervical cancer cells can bind and internalize goldlabeled MIS (19,20), suggesting that cervical cancer cells might express MIS receptor; however, a functional consequence of this interaction has not been formally shown until now. In this study, we demonstrate that three human cervical cancer cell lines and normal rat cervix express the MIS type II receptor and that MIS can inhibit the growth of the cancer cell lines tested.…”

Section: Mis Inhibits the Growth Of Ovarian Cancer Cells In Vitro Andmentioning

confidence: 99%

“…Despite a significant reduction in the annual cervical cancer death rate in the United States since the introduction of the Papanicolaou test (17), cervical cancer remains a major health threat in third world countries (18). Moreover, treatment of advanced disease with chemotherapy and radiation carries with it significant toxicity and often results in infertility among premenopausal women.In support of the idea that cervical cancer cells might be a target for MIS, Wang et al (19,20) demonstrated by electron microscopy that several cervical cancer cell lines (CaSki and HeLa) bind and internalize gold-labeled MIS ligand purified from avian testes. In addition, the spectrum of cell cycle defects in these cell lines is similar to that observed in OVCAR8 cells, which are sensitive to MIS (6).…”

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confidence: 99%

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Mullerian Inhibiting Substance inhibits cervical cancer cell growth via a pathway involving p130 and p107

Barbie

MacLaughlin

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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In addition to causing regression of the Mullerian duct in the male embryo, Mullerian Inhibiting Substance (MIS) inhibits the growth of epithelial ovarian cancer cells, which are known to be of Mullerian origin. Because the uterine cervix is derived from the same Mullerian duct precursor as the epithelium of the ovary, we tested the hypothesis that cervical cancer cells might also respond to MIS. A number of cervical cancer cell lines express the MIS type II receptor, and MIS inhibits the growth of both human papilloma virus-transformed and non-human papilloma virus-transformed cervical cell lines, with a more dramatic effect seen in the latter. As in the ovarian cancer cell line OVCAR8, suppression of growth of the C33A cervical cancer cell line by MIS is associated with induction of the p16 tumor suppressor protein. However, in contrast to OVCAR8 cells, induction of p130 and p107 appears to play an important role in the inhibition of growth of C33A cells by MIS. Finally, normal cervical tissue expresses the MIS type II receptor in vivo, supporting the idea that MIS could be a targeted therapy for cervical cancer.M ullerian Inhibiting Substance (MIS), also known as antiMullerian hormone, has long been known for its canonical activity of causing the regression of the embryonic Mullerian duct, the anlagen of the fallopian tubes, the surface epithelium of the ovaries, the uterus, the cervix, and the upper third of the vagina. Given the sensitivity of these tissues to MIS, we proposed that this 140-kDa hormone could inhibit the growth of Mullerian ductderived tumors and demonstrated that partially purified preparations of bovine MIS inhibited growth of an ovarian cancer cell line (1, 2) and of primary ovarian and endometrial cells in vitro (3, 4). Using more highly purified recombinant human MIS, we demonstrated growth inhibition of both human ovarian cancer cell lines and primary tumors in vitro and in vivo (5-8). Recently, we showed that the epithelial ovarian cancer cell line OVCAR8 expresses the MIS type II receptor and responds to MIS by growth inhibition mediated through a retinoblastoma protein (pRB)-independent mechanism involving the up-regulation of p16 (6). As a member of the INK4 family of cyclin-dependent kinase (CDK) inhibitors, p16 regulates the cell cycle by inhibiting the kinase activity of cyclin͞ CDK (CDK 4͞6) complexes (9), and induction of p16 is known to disrupt cell cycle progression and to regulate apoptosis (10-14).To study whether other Mullerian duct-derived tumors might be sensitive to MIS, we investigated its effect on human cervical cancer cell lines. The third most common neoplasm of the female genital tract, cervical cancer accounts for Ϸ10% of all cancers in women and resulted in 4,800 deaths in 1999 in the United States (15). A significant proportion of these cancers are due to infection with high risk subtypes of the human papilloma virus (HPV) (16). Despite a significant reduction in the annual cervical cancer death rate in the United States since the introduction of the Papanico...

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Section: Ullerian Inhibiting Substance (Mis) Also Known As Anti-mentioning

confidence: 99%

Section: Ullerian Inhibiting Substance (Mis) Also Known As Anti-mentioning

confidence: 99%

Section: Mis Inhibits the Growth Of Ovarian Cancer Cells In Vitro Andmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Mullerian Inhibiting Substance inhibits cervical cancer cell growth via a pathway involving p130 and p107

Barbie

MacLaughlin

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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“…Numerous studies have reported that the suppressive effect of MIS on ovarian cancer cells increases with the concentration of MIS/AMH (15)(16)(17)(18)(19)(20). There have been numerous reports of the anti-cancer effect of MIS/AMH on MIS/AMH receptor-presenting cervical cancer (21,22), breast cancer tissues and cells (23), and endometrial cancer (24,25).…”

Section: Introductionmentioning

confidence: 99%

M�llerian inhibiting substance/anti‑M�llerian hormone type II receptor protein and mRNA expression in the healthy and cancerous endometria

Kim

Lee

et al. 2018

Oncol Lett

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Müllerian inhibiting substance/anti-Müllerian hormone (MIS/AMH) is a regulator of the female reproductive system, an indicator of ovarian reserve and a growth inhibitor of Müllerian duct-derived tumors in vivo and in vitro. The objective of the present study was to analyze MIS/AMH type II receptor (MIS/AMHRII) protein and mRNA expression in healthy human endometria compared with patients with endometrial hyperplasia and endometrial cancer, providing a foundation for MIS/AMH as a biological modifier for treatment of endometrial hyperplasia and endometrial cancer. The present study included healthy endometrial tissues (n=20), simple endometrial hyperplasia tissues without atypia (n=17), complex endometrial hyperplasia tissues without atypia (n=24) and endometrial cancer tissues (n=8). The location and variation of MIS/AMHRII protein expression was observed by immunohistochemistry. The expression was graded by two pathologists and was categorized as follows: Negative, weakly positive, moderately positive or strongly positive. Reverse transcription-quantitative polymerase chain reaction was used to quantify MIS/AMHRII mRNA expression. The expression of MIS/AMHRII protein was observed in the cytoplasm of healthy human endometria, endometrial hyperplasia and endometrial cancer cells. The frequency of MIS/AMHRII protein expression was 20.22±10.35% in the proliferative phase of the healthy endometrium and 24.09±11.73% in the secretory phase of the healthy endometrium. However, no differences were observed in the menstrual cycle phases. The frequency was 54.50±16.59% in endometrial hyperplasia without atypia, 55.10±15.87% in endometrial hyperplasia with atypia and 73.88±15.70% in endometrial cancer, indicating that expression was enhanced as the disease progressed from healthy to malignant status. In endometrial hyperplasia, MIS/AMHRII protein expression was significantly associated with histological complexity compared with atypia status. The present study demonstrated that MIS/AMHRII is present in healthy endometria, endometrial hyperplasia and endometrial cancer. The low expression frequency of MIS/AMHRII was not significantly different among normal endometrial tissues, however, the protein expression was elevated in endometrial hyperplasia and endometrial cancer. These findings indicated that the study of bioactive MIS/AMH, as a possible treatment for tumors expressing the MIS/AMH receptor, is essential.

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Anti-Müllerian hormone is associated with extrauterine involvement and stage of disease in patients with endometrial cancer

Dogan

Kerimoğlu

Karabağlı

et al. 2014

Journal of Obstetrics and Gynaecology

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Our aim was to evaluate serum levels of anti-Müllerian hormone (AMH) and also immunohistochemical (IHC) staining properties of AMH receptor type II (AMHRII) in patients with endometrial cancer (EC) and a control group. Preoperatively, serum levels of AMH were assessed and AMHRII expression was evaluated by immunohistochemistry in a benign and malignant group. AMH serum levels of the control group and EC patients were comparable. For EC patients, there was no difference with respect to the AMH levels and tumour stage; grade; histological type; deep myometrial invasion; lymphovascular space invasion or lymph node involvement. However, AMH levels in patients with extrauterine involvement were higher than patients with disease confined to the uterus. EC samples were more likely to be stained positive for AMHRII than benign lesions. Also, as the stage of the lesion worsens, the rate of IHC staining of AMHRII decreases. In conclusion, AMHRII is expressed in normal endometrial cells as well as endometrial cancer cells. AMH levels increase in EC, with extrauterine involvement at least in locally advanced disease. Also AMH expression decreases as the disease is staged-up.

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Characterization of Mullerian inhibiting substance binding on cervical carcinoma cells demonstrated by immunocytochemistry

Cited by 5 publications

References 19 publications

Mullerian Inhibiting Substance inhibits cervical cancer cell growth via a pathway involving p130 and p107

Mullerian Inhibiting Substance inhibits cervical cancer cell growth via a pathway involving p130 and p107

M�llerian inhibiting substance/anti‑M�llerian hormone type II receptor protein and mRNA expression in the healthy and cancerous endometria

Anti-Müllerian hormone is associated with extrauterine involvement and stage of disease in patients with endometrial cancer

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