ERbB-2 expression is rate-limiting for epidermal growth factor-mediated stimulation of ovarian cancer cell proliferation

Hsieh, Susie S.; Malerczyk, Claudius; Aigner, Achim; Czubayko, Frank

doi:10.1002/(sici)1097-0215(20000601)86:5<644::aid-ijc7>3.0.co;2-t

Cited by 33 publications

(25 citation statements)

References 18 publications

(42 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Furthermore, it has been reported that EGFR-HER-2 heterodimers are rate-limiting in the EGF-mediated proliferation of tumour cells (Hsieh et al, 2000). These results suggested that EGFR and HER-2 may interact with each other and lead to effective antitumour activity.…”

Section: Discussionmentioning

confidence: 96%

Targeting EGFR and HER-2 with cetuximab- and trastuzumab-mediated immunotherapy in oesophageal squamous cell carcinoma

et al. 2007

View full text Add to dashboard Cite

We previously reported that oesophageal squamous cell carcinoma (SCC) had a relatively high incidence of EGFR and HER-2 overexpression. Thus, anti-HER family targeting may become a promising approach to treat oesophageal SCC. In the present study, we investigated (a) the distribution of EGFR and HER-2 expression in oesophageal SCC (n ¼ 66) detected by immunohistochemistry and (b) cetuximab-and/or trastuzumab-mediated biological activity (antiproliferative effect by the MTT assay, apoptosis-inducing activity by the annexin V/propidium iodide assay, and antibody-dependent cellular cytotoxicity (ADCC) by the 51 Cr-release assay) against oesophageal SCC cell lines with various levels of EGFR and HER-2. Twelve of the 66 patients (18%) showed both EGFR-and HER-2 expression. Out of both EGFR-and HER-2-positive cases, nine cases (75%) showed EGFR and HER-2 expression in individually distinct regions. Furthermore, the combination of cetuximab and trastuzumab could induce synergistic antiproliferative effects and additional ADCC activities against not all, but several oesophageal SCC cell lines with EGFR and HER-2 expression. The combination of cetuximab and trastuzumab may be useful in the treatment of oesophageal SCC with EGFR and HER-2 expression.

show abstract

Section: Discussionmentioning

confidence: 96%

Targeting EGFR and HER-2 with cetuximab- and trastuzumab-mediated immunotherapy in oesophageal squamous cell carcinoma

et al. 2007

View full text Add to dashboard Cite

show abstract

“…Given that SK-OV-3 ovarian cancer cells are characterized by HER2 overexpression (Hsieh et al 2000) determining their fast, hormone-independent growth, we also examined HER2 transcript levels subject to ICB-1 knockdown. After analysis of HER2 expression by real-time RT-PCR, we observed a slight, but significant decrease of HER2 mRNA levels in SK-OV/icbKD cells by about 25% (Fig.…”

Section: Knockdown Of Icb-1 Gene In Mcf-7 Breast Cancer and Sk-ov-3 Omentioning

confidence: 87%

Knockdown of ICB-1 gene enhanced estrogen responsiveness of ovarian and breast cancer cells

Konwisorz¹,

Springwald²,

Haselberger³

et al. 2010

Endocrine-Related Cancer

View full text Add to dashboard Cite

ICB-1 chromosome 1 open reading frame 38 (C1orf38) is a human gene initially described by our group to be involved in differentiation processes of cancer cells. Recently, we have reported ICB-1 as a novel estrogen target gene and identified an estrogen response element in its promoter. In this study, we examined the role of ICB-1 in regulation of proliferation of breast and ovarian cancer cells. We knocked down its expression in estrogen-dependent MCF-7 breast cancer cells and hormone-unresponsive SK-OV-3 ovarian cancer cells by stable transfection with a specific shRNA plasmid followed by G-418 selection. Knockdown of ICB-1 enabled a considerable estrogen response of SK-OV-3 cells in terms of proliferation. This transformation of SK-OV-3 cells into an estrogen-responsive phenotype was accompanied by upregulation of estrogen receptor a (ERa) expression and a significant decrease of ERb expression on the mRNA level. Expression of ERa-dependent genes progesterone receptor, pS2, fibulin 1c, and c-fos was elevated in SK-OV-3 cells stably expressing ICB-1 shRNA. In MCF-7 cells, ICB-1 knockdown exerted similar effects on gene expression, supporting a general role of ICB-1 in estrogen responsiveness. Our data suggest that differentiation-associated gene ICB-1 might exert antagonistic actions on cellular estrogen response, which can result in inhibition of estradiol-triggered proliferation. The molecular mechanisms mediating this inhibitory effect of ICB-1 on estrogen signaling are suggested to be limitation of ERa transcript levels but sustaining high levels of ERb, reducing both activation of ERa target genes and cellular proliferation. The identification of ICB-1 as a new player in endocrine-related cancer encourages further studies on the significance of this gene in cancer development and therapy.

show abstract

“…Yu et al (47) injected SKOV3 cells into immunodeficient mice, isolated a secondary cell line that expressed 2-fold greater levels of ErbB-2 than the parental SKOV3, and correlated this increased ErbB-2 expression with increased malignancy. Furthermore, Hsieh et al (48) created SKOV3 analogues with a range of reduced ErbB-2 expression and correlated increased ErbB-2 expression with an increase in EGFmediated proliferation. The model system described here also defines an SKOV3-derived cell line with increased ErbB-2 expression that correlates with the introduction and stimulation of LHR.…”

Section: Discussionmentioning

confidence: 99%

“…Up-regulation of ErbB-2 has been shown to increase proliferation, invasion, and migration in several human cancers (26,60), and studies in SKOV3 cells document a correlation between increased ErbB-2 protein expression and increased proliferation (47,48). However, in our SKOV3-based model system coexpressing LHR and ErbB-2, the LH-induced upregulation of ErbB-2 was insufficient in overcoming the negative effects of LHR on invasion, proliferation, or woundinduced migration and did not correlate with a more aggressive phenotype.…”

Section: Discussionmentioning

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

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

ERbB-2 expression is rate-limiting for epidermal growth factor-mediated stimulation of ovarian cancer cell proliferation

Cited by 33 publications

References 18 publications

Targeting EGFR and HER-2 with cetuximab- and trastuzumab-mediated immunotherapy in oesophageal squamous cell carcinoma

Targeting EGFR and HER-2 with cetuximab- and trastuzumab-mediated immunotherapy in oesophageal squamous cell carcinoma

Knockdown of ICB-1 gene enhanced estrogen responsiveness of ovarian and breast cancer cells

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

Contact Info

Product

Resources

About