Human ovarian surface epithelial (OSE) cells express LH/hCG receptors, and HCG inhibits apoptosis of OSE cells via up‐regulation of insulin‐like growth factor‐1

Kuroda, Hisao; Mandai, Masaki; Konishi, Ikuo; Tsuruta, Yuko; Kusakari, Takashi; Kariya, Masatoshi; Fujii, Shingo

doi:10.1002/1097-0215(200002)9999:9999<::aid-ijc1060>3.0.co;2-0

Cited by 62 publications

(53 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Epidemiologic evidence correlates physiologic conditions that lead to high gonadotropin levels with an increased risk of ovarian cancer (5). LHR is expressed in the putative precursor cell to ovarian cancer, the ovarian surface epithelium (OSE), and in 40% of ovarian cancers (8,12), although one study correlated a decreased expression of LHR with increasing grade of ovarian cancer (36). LHR is also expressed in other nongonadal tissues, such as brain, skin, and mammary gland (37)(38)(39).…”

Section: Discussionmentioning

confidence: 99%

“…Epidemiologic evidence implicates the pituitary-derived gonadotropic hormones, follicle-stimulating hormone (FSH) and LH, in the development of ovarian cancer by correlating an increased risk of ovarian cancer with physiologic conditions resulting in increased exposure to LH and FSH, such as incessant ovulation, infertility treatments, and menopause (4,5). In vivo, LH influences cellular processes, including adhesion (6), apoptosis (7,8), anchorage-independent growth (9), angiogenesis (10), and proliferation in ovarian cancer cells or in ovarian epithelial cells, the putative precursor cell to epithelial ovarian cancer (11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Luteinizing Hormone–Induced Up-Regulation of ErbB-2 Is Insufficient Stimulant of Growth and Invasion in Ovarian Cancer Cells

Warrenfeltz

Lott

Palmer

et al. 2008

Molecular Cancer Research

View full text Add to dashboard Cite

The effects of luteinizing hormone (LH), a gonadotropic hormone implicated in the development of ovarian cancer, are mediated by specific binding to its G protein -coupled receptor, the LH receptor (LHR). Activated LHR initiates second messenger responses, including cyclic AMP (cAMP) and inositol phosphate. Because cAMP increases expression of ErbB-2, a receptor tyrosine kinase whose overexpression in cancers correlates with poor survival, we hypothesized that LH may regulate ErbB-2 expression. Cell surface LHR expression in stable transformants of the ErbB-2 -overexpressing ovarian cancer cell line SKOV3 was confirmed by PCR and whole-cell ligand binding studies. Second messenger accumulation in the LHR-expressing cells confirmed signaling through Gs and Gq. Western blots of total protein revealed that LHR introduction up-regulated ErbB-2 protein expression 2-fold and this was further up-regulated in a time-and dose-dependent manner in response to LH. Forskolin and 8Br-cAMP also up-regulated ErbB-2 in both LHR-expressing and mock-transfected cells, indicating that regulation of ErbB-2 is a cAMP-mediated event. Kinase inhibitor studies indicated the involvement of protein kinase A -mediated, protein kinase C -mediated, epidermal growth factor receptor -mediated, and ErbB-2 -mediated mechanisms. The LH-induced up-regulation of ErbB-2 was insufficient to overcome the negative effects of LH on proliferation, invasion, and migration. A molecular signature for this nonaggressive phenotype was determined by Taqman array to include increased and decreased expression of genes encoding adhesion proteins and metalloproteinases, respectively. These data establish a role for LH and LHR in the regulation of ErbB-2 expression and suggest that, in some systems, ErbB-2 up-regulation alone is insufficient in producing a more aggressive phenotype.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Luteinizing Hormone–Induced Up-Regulation of ErbB-2 Is Insufficient Stimulant of Growth and Invasion in Ovarian Cancer Cells

Warrenfeltz

Lott

Palmer

et al. 2008

Molecular Cancer Research

View full text Add to dashboard Cite

show abstract

“…25,26 Specific binding activity of hCG in NOSE cells has been shown to inhibit apoptosis via upregulation of insulin-like growth factor-1. 27 The presence of hCG in BPE may have led to reduced apoptosis, which could explain why BPE had such a positive effect on growth and in particular the cloning efficiency of NOSE cells. It will be necessary to grow NOSE cells in media conditioned with hCG alone to confirm this.…”

Section: Discussionmentioning

confidence: 99%

A modified medium that significantly improves the growth of human normal ovarian surface epithelial (OSE) cells in vitro

Wilbanks

Balkwill

et al. 2004

Laboratory Investigation

View full text Add to dashboard Cite

Approximately 90% of malignant ovarian tumours are epithelial and thought to arise from a single cell layer, the ovarian surface epithelium. In culture, human normal ovarian surface epithelial (OSE) cells have a very limited lifespan before they senesce, rarely progressing beyond 10 population doublings. This has restricted the use of normal OSE cells for studying the biology of ovarian surface epithelium and identifying molecular events that contribute to malignant transformation. We have investigated the conditions for culturing human, normal OSE cells in vitro using modified media. Culturing normal OSE cells in a modified medium (NOSE-CM) supplemented with epidermal growth factor, hydrocortisone, insulin and bovine pituitary extract led to significant improvements in the seeding and cloning efficiencies, overall cell growth and lifespan compared to culturing in a basic, nonsupplemented medium (BM) and previously used media (F-12 K medium and William's medium E). Cells cultured in NOSE-CM underwent, on an average, 19.0 population doublings (95% CI 16.3-21.7); cells cultured in BM underwent 0.43-3.52 population doublings over a similar time period. Growth curves established for different lines indicated that OSE cells continued to grow beyond passage 11 and up to passage 18 in NOSE-CM, but never beyond passage 7 when cultured in BM. It is likely that establishing optimal conditions for the growth of OSE cells in vitro will enable studies of the biological and genetic mechanisms of transformation in epithelial ovarian cancers.

show abstract

“…Among the ovarian tumors, those of granulosa cell origin are rare, 3.0% -7.6% of primary ovarian tumors, but the life expectancy after treatment is short in comparison to other ovarian cancers (Cronje et al 1999, Crayford et al 2000, the tumor-related mortality rate is 37.3% (Cronje et al 1999), and approximately 80% of patients die of recurrent disease (Young et al 1984, Cronje et al 1999. The majority of human ovarian cancers are ovarian surface epithelial tumors, and 70% of them are shown to express LHR (Mandai et al 1997, Konishi et al 1999, Lu et al 2000, Auersperg et al 2001, Kuroda et al 2001). …”

Section: Gonadal Somatic Cell Tumors and Lhrmentioning

confidence: 99%

Use of hecate–chorionic gonadotropin β conjugate in therapy of lutenizing hormone receptor expressing gonadal somatic cell tumors

Rivero-Müller¹,

Vuorenoja²,

Tuominen³

et al. 2007

Molecular and Cellular Endocrinology

View full text Add to dashboard Cite

Human ovarian surface epithelial (OSE) cells express LH/hCG receptors, and HCG inhibits apoptosis of OSE cells via up‐regulation of insulin‐like growth factor‐1

Cited by 62 publications

References 29 publications

Luteinizing Hormone–Induced Up-Regulation of ErbB-2 Is Insufficient Stimulant of Growth and Invasion in Ovarian Cancer Cells

Luteinizing Hormone–Induced Up-Regulation of ErbB-2 Is Insufficient Stimulant of Growth and Invasion in Ovarian Cancer Cells

A modified medium that significantly improves the growth of human normal ovarian surface epithelial (OSE) cells in vitro

Use of hecate–chorionic gonadotropin β conjugate in therapy of lutenizing hormone receptor expressing gonadal somatic cell tumors

Contact Info

Product

Resources

About