Regulation of growth of normal ovarian epithelium and ovarian cancer cell lines by transforming growth factor-β

Berchuck, A.; Rodriguez, G.; Olt, George J.; Arrick, Bradley A.; Clarke‐Pearson, Daniel L.; Bast, R

doi:10.1016/0090-8258(91)90173-3

Cited by 5 publications

(9 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In normal ovarian surface epithelial cells, autocrine growth inhibition is maintained by TGFβ75. In approximately 40% of ovarian cancers, expression of or responsiveness to TGFβ is lost.…”

Section: Tumour Biologymentioning

confidence: 99%

The biology of ovarian cancer: new opportunities for translation

2009

View full text Add to dashboard Cite

Over the past two decades, the 5-year survival for ovarian cancer patients has substantially improved owing to more effective surgery and treatment with empirically optimized combinations of cytotoxic drugs, but the overall cure rate remains approximately 30%. Many investigators think that further empirical trials using combinations of conventional agents are likely to produce only modest incremental improvements in outcome. Given the heterogeneity of this disease, increases in longterm survival might be achieved by translating recent insights at the molecular and cellular levels to personalize individual strategies for treatment and to optimize early detection.• Several factors make ovarian cancer a difficult disease to treat effectively. Although many patients experience symptoms, these often overlap with other ailments, and many patients are diagnosed after the cancer has metastasized. Ovarian cancer is also heterogeneous -multiple genetic and epigenetic changes are evident in patients with ovarian cancer; however, how such changes are selected for during tumorigenesis is not yet clear.• Mutation and loss of TP53 function is one of the most frequent genetic abnormalities in ovarian cancer and is observed in 60-80% of both sporadic and familial cases. Of the 16 candidate tumour suppressor genes identified to date in ovarian cancer, 3 are imprinted genes. Several growth inhibitory genes are also silenced by methylation or imprinting.• Inheritance of DNA repair defects contributes to as many as 10-15% of ovarian cancers. The lifetime risk of developing ovarian cancer in mutation carriers varies with the genetic defect (for BRCA1 30-60%, for BRCA2 15-30% and for hereditary non-polyposis colon cancer 7%).• At least 15 oncogenes have been implicated in ovarian cancers, and DNA copy number abnormalities have also been found in loci that are known to contain noncoding microRNAs. At least seven signalling pathways are activated in >50% of ovarian cancers, and mutations that affect cell proliferation, apoptosis and autophagy are also evident.• Ovarian cancer can be split into two groups on the basis of genetic changes: low-grade tumours with mutations in KRAS, BRAF and PIK3CA, loss of heterozygosity (LOH) on chromosome Xq, microsatellite instability and expression of amphiregulin; and high-grade tumours with aberrations in TP53 and potential aberrations in BRCA1 and BRCA2, as well as LOH on chromosomes 7q and 9p.Correspondence to: Robert C. Bast, Jr 1 rbast@mdanderson.org. Competing interests statementThe authors declare no competing financial interests. NIH Public Access Author ManuscriptNat Rev Cancer. Author manuscript; available in PMC 2010 February 1. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript• Changes in cell adhesion and motility also contribute to disease development and metastasis. Adhesion of ovarian cancer cells to the mesothelial cells and to the underlying stroma is mediated by CD44, CA125 and b1 intergrin on the surface of ovarian cancer cells that bind to mesotheli...

show abstract

Section: Tumour Biologymentioning

confidence: 99%

The biology of ovarian cancer: new opportunities for translation

2009

View full text Add to dashboard Cite

show abstract

“…TGF‐β is a multifunctional protein endowed with a broad range of biological activities on cells of different lineages 8 . Secretion of TGF‐β has been detected from normal and neoplastic human ovarian epithelium, as well as a wide variety of other tumours 8,9 . The predominant effect of TGF‐β on most normal cells in vitro is reported to be inhibition of proliferation 8,9 .…”

Section: Introductionmentioning

confidence: 99%

Increased levels of interleukin-10 and transforming growth factor-beta in the plasma and ascitic fluid of patients with advanced ovarian cancer

Santin

Bellone

Ravaggi

et al. 2001

BJOG: An Internal Journal of Obs Gyn

View full text Add to dashboard Cite

aObjectives To assess expression of the immunosuppressive cytokines IL-10 and TGF-b in the ascitic¯uid and plasma of advanced ovarian cancer patients. Design A prospective study.Setting The Department of Obstetrics and Gynaecology at the University of Arkansas for Medical Sciences.Population Twenty-eight women diagnosed with advanced ovarian cancer and ten normal female controls. Methods Plasma and ascitic samples were collected at the time of surgery and analysed for the presence of IL-10 and TGF-b using a sensitive enzyme-linked immunosorbent assay. Results Elevated levels of IL-10 were detected in the plasma [mean (SD) 12 (5) . Surprisingly, however, although elevated TGF-b levels were also detected in the peritoneal¯uid of all ovarian cancer patients [mean (SD) 407 (158) pg/mL; range 140 to 770 pg/mL], these levels were signi®cantly lower than those seen in matched plasma samples (P , 0.001).Conclusions Local and systemic secretion of immunosuppressive cytokines may play an important role in the impaired anti-tumour immune function commonly observed in advanced ovarian cancer. However, the observation that plasma levels of TGF-b are signi®cantly higher than those detected in the ascitic¯uid raises the possibility that cells other than tumour cells are responsible for TGF-b release in the bloodstream of these patients.

show abstract

“…TGF‐β has been shown to up‐regulate p21 WAF1 in immortalized epithelial ovarian carcinoma cells under certain conditions 6, 11. It had been previously shown that TGF‐β may inhibit cellular growth by inducing p21 WAF1 through the p53 pathway.…”

Section: Discussionmentioning

confidence: 99%

“…Previously, it has been shown that a majority of immortalized epithelial ovarian carcinoma cells had lost the ability to respond to the inhibitory effect of TGF‐β 6, 11. However, a very small number of immortalized ovarian carcinoma cells did manage to maintain their sensitivity to the inhibitory effect of TGF‐β.…”

mentioning

confidence: 99%

“…However, a very small number of immortalized ovarian carcinoma cells did manage to maintain their sensitivity to the inhibitory effect of TGF‐β. It is thought that up‐regulation of p21 WAF1 mRNA may be a factor involved in this response 6, 11. Furthermore, this mechanism is thought to be independent of the p53 pathway because p53 mutations did not confer resistance to the inhibitory effect of TGF‐β as noted for other cell systems 6, 11…”

mentioning

confidence: 99%

See 1 more Smart Citation