Decreased expression of the c-kit receptor is associated with increased apoptosis in subfertile human testes

Feng, Huai L.; Sandlow, Jay; Sparks, Amy E.T.; Sandra, Alexander; Zheng, Lei

doi:10.1016/s0015-0282(98)00401-4

Cited by 74 publications

(49 citation statements)

References 19 publications

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“…We speculate that KIT suppression of p53 in the testes is mediated through regulation of MAGE expression and MAGE binding to KAP1. We also note that KIT seems to be relevant to human fertility because decreased KIT expression is seen in testes of subfertile adult humans and is associated with increased apoptosis in spermatocytes (36).…”

Section: Discussionmentioning

confidence: 76%

MAGE-A, mMage-b, and MAGE-C Proteins Form Complexes with KAP1 and Suppress p53-Dependent Apoptosis in MAGE-Positive Cell Lines

Yang¹,

O'Herrin²,

Wu³

et al. 2007

Cancer Research

238

203

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The MAGE-A, MAGE-B, and MAGE-C protein families comprise the class-I MAGE/cancer testes antigens, a group of highly homologous proteins whose expression is suppressed in all normal tissues except developing sperm. Aberrant expression of class I MAGE proteins occurs in melanomas and many other malignancies, and MAGE proteins have long been recognized as tumor-specific targets; however, their functions have largely been unknown. Here, we show that suppression of class I MAGE proteins induces apoptosis in the Hs-294T, A375, and S91 MAGE-positive melanoma cell lines and that members of all three families of MAGE class I proteins form complexes with KAP1, a scaffolding protein that is known as a corepressor of p53 expression and function. In addition to inducing apoptosis, MAGE suppression decreases KAP1 complexing with p53, increases immunoreactive and acetylated p53, and activates a p53 responsive reporter gene. Suppression of class I MAGE proteins also induces apoptosis in MAGE-Apositive, p53wt/wt parental HCT 116 colon cancer cells but not in a MAGE-A-positive HCT 116 p53 À/À variant, indicating that MAGE suppression of apoptosis requires p53. Finally, treatment with MAGE-specific small interfering RNA suppresses S91 melanoma growth in vivo, in syngenic DBA2 mice. Thus, class I MAGE protein expression may suppress apoptosis by suppressing p53 and may actively contribute to the development of malignancies and by promoting tumor survival. Because the expression of class I MAGE proteins is limited in normal tissues, inhibition of MAGE antigen expression or function represents a novel and specific treatment for melanoma and diverse malignancies. [Cancer Res 2007;67(20):9954-62]

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Section: Discussionmentioning

confidence: 76%

MAGE-A, mMage-b, and MAGE-C Proteins Form Complexes with KAP1 and Suppress p53-Dependent Apoptosis in MAGE-Positive Cell Lines

Yang¹,

O'Herrin²,

Wu³

et al. 2007

Cancer Research

238

203

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“…This side effect of diabetes can be due to interference with performance of interstitial endocrine cells (Leydig cells) (Ferlin et al, 2008;Feng et al, 1999). Maneesh et al (2006) and Stanciu et al (2010) Hypothalamus-Pituitary-gonadal axis in males and decreased testosterone significantly.…”

Section: Discussionmentioning

confidence: 99%

Tribulus terrestris Hydroalcoholic Extract Administration Effects on Reproductive Parameters and Serum Level of Glucose in Diabetic Male Rats

et al. 2016

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GHANBARI, A.; MORADI, M.; RAOOFI, A.; FALAHI, M. & SEYDI, S.Tribulus terrestris hydroalcoholic extract administration effects on reproductive parameters and serum level of glucose in diabetic male rats. Int. J. Morphol.,34(2):796-803, 2016. SUMMARY:Usage of medicinal plants for the treatment of diseases is a remarkable strategy considered in both clinical and experimental studies. This study was conducted to evaluate the effect of Tribulus terrestris hydroalcoholic extract administration on the serum level of glucose and reproductive parameters in diabetic male rats. In this experimental study, 30 adult male Wistar rats (200-250 g) were divided into 5 groups (n= 6). Diabetes was induced by a single intraperitoneal injection of 50 mg/kg streptozotocin. Experimental groups received daily Intraperitoneal injection of the extract (100, 250 and 500 mg/kg) since one week after inducing diabetes for two weeks. At the end of the experiment, the serum levels of testosterone and glucose were examined by ELISA and Glucodr devices respectively. Sperm parameters including morphology, count and motility were evaluated from the cauda epididymis. The diameters of seminiferous tubules were assessed based on 5 µm paraffin section of H&E stained section of testes. The data were evaluated by One Way ANOVA followed by post-hoc test using SPSS software. In T. terrestris extract groups, there were significant reductions in the levels of blood glucose while increased sperm motility, sperm count and seminiferous tubules diameter, percentage of sperms with normal morphology, level of testosterone hormone and final body weight compared with diabetic group (p <0.001). In conclusion, T. terrestris hydroalcoholic extract decreases serum level of glucose and diminishes the side effects of diabetes on male reproductive system showing by increasing in the serum level of testosterone, improving sperm parameters and returning the seminiferous tubules to normal diameter by a dose dependent manner.

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“…SCF is a ligand of the proto-oncogene c-KIT which acts as a tyrosine kinase [Strohmeyer et al, 1995]. The SCF/c-KIT system plays an important role, not only in fetal germ cell migration as mentioned above but also in their proliferation and apoptosis as well as in regulation of adult spermatogonia proliferation and maintenance [Strohmeyer et al, 1995;Feng et al, 1999;Maduit et al, 1999;Hoei-Hansen, 2008;Stoop et al, 2008]. In the adult testis, SCF is synthesized by Sertoli cells in 2 splice variants -the membrane-bound form acts in establishing and maintaining germ cells, and the soluble form induces the testosterone production in Leydig cells [Maduit et al, 1999].…”

Section: How To Identify a Gonad At Risk For Development Of Malignancmentioning

confidence: 99%

Tumor Risk in Disorders of Sex Development

Pleskacova

Hersmus

Oosterhuis

et al. 2010

Sex Dev

159

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Certain patients with disorders of sex development (DSD), who bear Y chromosome material in their karyotype, are at increased risk for the development of type II germ cell tumors (GCT), which arise from early fetal germ cells. DSD gonads frequently harbor immature germ cells which express early fetal germ cell markers. Some of them (e.g. OCT3/4 and NANOG) seem to be of pathogenetic relevance in GCT development providing cells with the ability of pluripotency, proliferation and apoptosis suppression. Also TSPY (testis-specific protein Y-encoded), the main candidate for the so-called gonadoblastoma locus on Y chromosome, is overexpressed in germ cells of DSD patients and possibly contributes to their survival and proliferation. Nowadays, the use of immunohistochemical methods is highly relevant in identifying DSD gonads at risk. The risk for GCT development varies. While the prevalence of GCT is 15% in patients with partial androgen insensitivity, it may reach more than 30% in patients with gonadal dysgenesis. Patients with complete androgen insensitivity and ovotesticular DSD develop malignancies in 0.8% and 2.6% of cases, respectively. However, these data may be biased for various reasons. To better estimate the risk in individual groups of DSD, further investigations on large patient series are needed.

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Decreased expression of the c-kit receptor is associated with increased apoptosis in subfertile human testes

Cited by 74 publications

References 19 publications

MAGE-A, mMage-b, and MAGE-C Proteins Form Complexes with KAP1 and Suppress p53-Dependent Apoptosis in MAGE-Positive Cell Lines

MAGE-A, mMage-b, and MAGE-C Proteins Form Complexes with KAP1 and Suppress p53-Dependent Apoptosis in MAGE-Positive Cell Lines

Tribulus terrestris Hydroalcoholic Extract Administration Effects on Reproductive Parameters and Serum Level of Glucose in Diabetic Male Rats

Tumor Risk in Disorders of Sex Development

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