Ovarian Carcinomas: CCN Genes Are Aberrantly Expressed and CCN1 Promotes Proliferation of these Cells

Autor: Hani Gabra, Dong Xie, Carl W. Miller, William S. Yi, Dong Yin, Miriam L. Popoviciu, Heming Wang, H. Phillip Koeffler, Diane Scott, J. W. Said, Sigal Gery
Rok vydání: 2005
Předmět:
Adult
Cancer Research
endocrine system diseases
Angiogenesis
medicine.medical_treatment
Blotting
Western
Transplantation
Heterologous
Mice
Nude
Apoptosis
Biology
Transfection
Carboplatin
Immediate-Early Proteins
Mice
Cell Line
Tumor
medicine
Animals
Humans
Protein Isoforms
RNA
Small Interfering
Protein kinase B
Aged
Cell Proliferation
Aged
80 and over
Ovarian Neoplasms
Reverse Transcriptase Polymerase Chain Reaction
Cell growth
Growth factor
Epithelial Cells
Neoplasms
Experimental
Middle Aged
Blotting
Northern
medicine.disease
Immunohistochemistry
female genital diseases and pregnancy complications
Gene Expression Regulation
Neoplastic
Oncology
Cell culture
Cancer research
Intercellular Signaling Peptides and Proteins
Female
Ectopic expression
Cisplatin
Signal transduction
Ovarian cancer
Neoplasm Transplantation
Cysteine-Rich Protein 61
Zdroj: Clinical Cancer Research. 11:7243-7254
ISSN: 1557-3265
1078-0432
DOI: 10.1158/1078-0432.ccr-05-0231
Popis: Purpose: The connective tissue growth factor/cysteine-rich 61/nephroblastoma overexpressed (CCN) family consists of six matricellular proteins that are involved in various cellular functions, such as proliferation, development, and angiogenesis. The purpose of this study was to explore the possibility that CCN genes are involved in ovarian cancers. Experimental Design: We quantified CCN expression in a series of 59 ovarian cancers using quantitative real-time reverse transcription-PCR. CCN1 protein levels were further determined by immunohistochemistry and Western blot analysis. Overexpression and inhibition of CCN1 expression by small interfering RNA were used to examine its role in ovarian cancer cell proliferation in vitro and in vivo. Results: We found dysregulation of levels of the various CCN mRNAs in ovarian cancers compared with their expression in normal whole ovaries. Expression of CCN1 protein was detected in normal ovarian epithelial cells and ovarian tumors as well as in ovarian cancer cell lines. Furthermore, estrogen increased CCN1 mRNA and protein levels in ovarian cancer cells. Ectopic expression of CCN1 enhanced the growth of ovarian cancer cells in liquid culture, whereas inhibition of its expression decreased proliferation and increased apoptosis in these cells. The observed changes in cell growth were accompanied with activation of Akt and extracellular signal-regulated kinase (ERK) signaling pathways. Stable expression of CCN1 in SKOV3 cells significantly increased tumorigenicity in nude mice. Finally, overexpression of CCN1 conferred resistant to carboplatin-induced apoptosis in SKOV3 cells. Conclusions: This is the first study to show abnormalities in CCN expression in ovarian carcinomas. Furthermore, our results suggest that CCN1 may play a role in ovarian carcinogenesis by stimulating survival and antiapoptotic signaling pathways.
Databáze: OpenAIRE
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