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WISP2 (Wnt-1-inducible signaling parthway protein-2)

Written2004-12Sushanta K. Banerjee, Snigdha Banerjee
Division of Hematology/Oncology, Depatment of Medicine,, Department of Anatomy, Cell Biology University of Kansas Medical Center, Research Director, Cancer Research Unit, VA Medical Center, Kansas City, MO 64128, USA

(Note : for Links provided by Atlas : click)


Alias (NCBI)CCN5
LocusID (NCBI) 8839
Atlas_Id 42814
Location 20q13.12  [Link to chromosome band 20q13]
Location_base_pair Starts at and ends at bp from pter
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
APPBP2 (17q23.2)::WISP2 (20q13.12)
Note WISP-2 is a member of the connective tissue growth factor/cysteine-rich 61/nephroblastoma overexpressed (nov) (CCN) family and is upregulated in the mouse mammary epithelial cell line C57MG transformed by Wnt-1 and in several non-invasive human breast tumor cell lines. WISP-2 is a serum and PMA (phorbol 12-myristate 13-acetate)-induced early responsive gene. Blocking the expression of this gene by WISP-2 antisense oligos or siRNA drastically reduce serum or PMA-induced cell proliferation in MCF-7 cells. Therefore, these studies suggest that WISP-2 signaling may be essential for mitogen-induced breast tumor cell proliferation.

WISP-2 expression is enhanced by important modulators of human breast cancer cell proliferation such as estrogen, progesterone and epidermal growth factor ( EGF) in MCF-7 cells. These effects, inhibited by appropriate antagonists, indicate that steroids and growth factor-induced upregulation of WISP-2 may be mediated through receptors.

The expression profile of WISP-2 gene in breast tumor biopsy tissue specimens are similar with that of in vitro studies and suggest that WISP-2 mRNA and protein levels are significantly higher in tumor samples as compared to the normal breast samples, and this expression is significantly correlated with the expression of estrogen receptor protein. However, within the tumor specimens, expression was predominant in the non-invasive carcinoma lesions as well as benign hyperplastic areas adjacent to the invasive tumors. Together, these findings suggest that bi-phasic regulation of WISP-2 signaling may be critical for initial events of growth, survivability and invasion of breast tumor cells.

WISP-2 also acts as a negative regulator in some cells including vascular smooth muscle cells.


Note Until now, three genes have been identified and isolated as members of WISP sub-family. WISP-1/CCN4, WISP-2/CCN5 and WISP-3/CCN6 genes were localized in human chromosomes 8q24.1-q24.3, 20q12-q13 and 6q22-23, respectively and exhibit tissue specific patterns of expression. Nucleotide and protein sequence alignment studies have demonstrated a 30-40% sequence homology within WISP genes and their modular architecture is similar except in their C-terminal domains, which is absent in the WISP-2 gene.
  Modular structure of individual genes of WISP sub-family of CCN family. Module shown with color boxes are the predicted primary translational.


Description The translation products of most of the CCN family members are secreted proteins of 35-40 kDa and have been shown to contain four distinct structural modules: 1) an IGF-binding protein type (IGFBP) domain, 2) a Von Willebrand type C (VWC) domain; 3) a Thrombospondin-1 (TSP-1) domain and 4) a C-terminal Cysteine-knot (CT) domain (10). Although the functional roles of these multiple modules are unclear, they raise interesting questions as to the contribution of each individual module to the biological properties of the full-length proteins.
Expression Epithelial cells and vascular smooth muscle cells
Localisation Adrenal gland, breast, colon, pancreas, uterus and ovary.
Function Positive regulator of epithelial cells and negative regulator of vascular smooth muscle cells.


Somatic Amplified in breast tumor cells.

Implicated in

Disease Breast cancer
Disease Colon cancer
Disease Macronodular adrenal hyperplasia


WISP-2 gene in human breast cancer: estrogen and progesterone inducible expression and regulation of tumor cell proliferation.
Banerjee S, Saxena N, Sengupta K, Tawfik O, Mayo MS, Banerjee SK
Neoplasia (New York, N.Y.). 2003 ; 5 (1) : 63-73.
PMID 12659671
Gene array analysis of macronodular adrenal hyperplasia confirms clinical heterogeneity and identifies several candidate genes as molecular mediators.
Bourdeau I, Antonini SR, Lacroix A, Kirschner LS, Matyakhina L, Lorang D, Libutti SK, Stratakis CA
Oncogene. 2004 ; 23 (8) : 1575-1585.
PMID 14767469
Estrogen-induced genes, WISP-2 and pS2, respond divergently to protein kinase pathway.
Inadera H
Biochemical and biophysical research communications. 2003 ; 309 (2) : 272-278.
PMID 12951045
Identification and cloning of a connective tissue growth factor-like cDNA from human osteoblasts encoding a novel regulator of osteoblast functions.
Kumar S, Hand AT, Connor JR, Dodds RA, Ryan PJ, Trill JJ, Fisher SM, Nuttall ME, Lipshutz DB, Zou C, Hwang SM, Votta BJ, James IE, Rieman DJ, Gowen M, Lee JC
The Journal of biological chemistry. 1999 ; 274 (24) : 17123-17131.
PMID 10358067
The growth arrest-specific gene CCN5 is deficient in human leiomyomas and inhibits the proliferation and motility of cultured human uterine smooth muscle cells.
Mason HR, Lake AC, Wubben JE, Nowak RA, Castellot JJ Jr
Molecular human reproduction. 2004 ; 10 (3) : 181-187.
PMID 14981145
WISP genes are members of the connective tissue growth factor family that are up-regulated in wnt-1-transformed cells and aberrantly expressed in human colon tumors.
Pennica D, Swanson TA, Welsh JW, Roy MA, Lawrence DA, Lee J, Brush J, Taneyhill LA, Deuel B, Lew M, Watanabe C, Cohen RL, Melhem MF, Finley GG, Quirke P, Goddard AD, Hillan KJ, Gurney AL, Botstein D, Levine AJ
Proceedings of the National Academy of Sciences of the United States of America. 1998 ; 95 (25) : 14717-14722.
PMID 9843955
Differential expression of WISP-1 and WISP-2 genes in normal and transformed human breast cell lines.
Saxena N, Banerjee S, Sengupta K, Zoubine MN, Banerjee SK
Molecular and cellular biochemistry. 2001 ; 228 (1-2) : 99-104.
PMID 11855747


This paper should be referenced as such :
Banerjee, SK ; Banerjee, S
WISP2 (wnt-1-inducible signaling parthway protein-2)
Atlas Genet Cytogenet Oncol Haematol. 2005;9(1):15-16.
Free journal version : [ pdf ]   [ DOI ]

External links

Genomic and cartography
Gene and transcription
RefSeq transcript (Entrez)
BioGPS (Tissue expression)8839
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Protein Interaction databases
Ontologies - Pathways
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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