Microcell-mediated transfer of chromosome 11 into ovarian carcinoma cell line, SKOV-3 results in suppression of tumorigenicity in scid/scid mice providing evidence from functional aspect that chromosome 11 carries ovarian tumor suppressor gene(s).

To identify the differentially expressed transcripts associated with suppression of tumorigenicity, cDNA from the tumorigenic clones were subtracted from the non-tumorigenic clones which were then either cloned, sequenced and searched in GenBank, or analyzed by Gene Discovery Array Screening (GDAS). A cDNA transcript corresponding to the gene Thy-1 located (11q23-24) was found to be exclusively expressed in the non-tumorigenic clones. Transfection of Thy-1-antisence to the non-tumorigenic clone, 11(H)9-8, abolished the Thy-1 expression and restored tumorigenicity in scid/scid mice. We therefore, hypothesize that Thy-1 is a putative ovarian tumor suppressor gene (TSG).

To test this hypothesis, the following studies are ongoing: 1) To verify the tumor suppressing nature of Thy-1 and its specificity in fresh/frozen ovarian tumors by Northern blot, immunocytochemistry, and flow cytometry followed by statistical correlation study; 2) To define the effect of Thy-1 on in vivo growth and tumorigenicity by comparative xenographic study in scid/scid between 11(C)9-8-Thy-1-antisense and 11(C)9-8-null, as well as SKOV-3-Thy-1 and SKOV-3-null; 3) To identify the downstream genes associated with Thy-1 by comparative macroarray and microarray analysis combined with suppression subtractive hybridization on the DNA population between SKOV-3-Thy-1 and SKOV-3-null, as well as 11(C)9-8-Thy-1-antisense and 11(C)9-8-null; 4) To identify the sequential signaling pathway of Thy-1 using the in vitro doxycyclin (dox) Thy-1 inducible system established in our laboratory. cDNA obtained from SKOV-3-Thy-1-inducible cells at various time post dox exposure will be analyzed and compared between adjacent time points by both macroarray and dual color microarray.

The accomplishment of this study cannot only verify the OVC tumor suppressing nature of Thy-1, but also let us understand the function of this important cell surface marker.

Katzman PJ, Wang B, Sawhney M, Wang N. Differential detection of deletion 22q11.2 syndrome by specialty and indication. Pediatr Dev Pathol. 2005 Sep-Oct;8(5):557-67. Epub 2005 Oct 12. (PubMed)

Lung HL, Bangarrusamy DK, Xie D, Cheung AKL, Cheng Y, Kumaran MK, Miller L, Liu ETB, Guan XY, Sham JS, Fang Y, Li L, Wang N, Protopopov AI, Zabarovsky ER, Tsao SW, Stanbridge EJ, Lung ML. THY1 is a candidate tumour suppressor gene with decreased expression in metastatic nasopharyngeal carcinoma. Oncogene. 2005 Sep 29;24(43):6525-32. (PubMed)

Abeysinghe HR, Li LQ, Guckert NL, Reeder J, Wang N. THY-1 induction is associated with up-regulation of fibronectin and thrombospondin-1 in human ovarian cancer. Cancer Genet. Cytogenet. 2005 Sep;161(2):151-8. (PubMed)

Abeysinghe HR, Pollock SJ, Guckert NL, Veyberman Y, Keng P, Halterman M, Federoff HJ, Rosenblatt JP, Wang N. The role of the THY1 gene in human ovarian cancer suppression based on transfection studies. Cancer Genet Cytogenet 149(1):1-10 (2004). (PubMed)

Patel D, Incassati A, Wang N, McCance DJ. Human papillomavirus type 16 E6 and E7 cause polyploidy in human keratinocytes and up-regulation of G2-M-phase proteins. Cancer Res 64(4):1299-306 (2004). (PubMed).

Segel GB, Woodlock TJ, Xu J, Li L, Felgar RE, Ryan DH, Lichtman MA, Wang N. Early gene activation in chronic leukemic B lymphocyters induced toward a plasma cell phenotype. Blood Cells Mol Dis 30(3):277-87 (2003). (PubMed)

Abeysinghe HR, Cao Q, Pollock S, Veyberman Y, Guckert NL, Keng P, Wang N. Thy-1 expression is associated with tumor suppression of human ovarian cancer. Cancer Genet Cytogenet 142:1-8 (2003). (PubMed)

Komrokji R, Lancet J, Felgar R, Wang N, Bennett JM. Burkitt’s leukemia with precursor B-cell immunophenotype and atypical morphology (atypical Burkitt’s leukemia/lymphoma): case report and review of literature. Leukemia Res 1641:1-7 (2003). (PubMed)

Wang N. Cytogenetics and molecular genetics of ovarian cancer. Am J Med Genet 2002 Oct 30;115(3):157-63. (PubMed)

Wang N. Methodologies in cancer cytogenetics and molecular cytogenetics. Am J Med Genet 2002 Oct 30;115(3):118-24. (PubMed)

Cao Q, Abeysinghe H, Chow O, Xu J, Kaung H, Fong C, Keng P, Insel RA, Lee WM, Barrett JC, Wang N. Suppression of tumorigenicity in human ovarian carcinoma cell line SKOV-3 by microcell-mediated transfer of chromosome 11.Cancer Genet.Cytogenet. 2001 Sep;129(2):131-7. (PubMed)

Rowe JM, Rapoport AP, Ryan DH, Nilsson BI, Duerst RE, Packman CH, Abboud CN, DiPersio JF, Linder T, Wang N, Simonsson B, Liesveld JL. Treatment of chronic myelogenous leukemia with autologous bone marrow transplantation followed by roquinimex. Bone Marrow Transplant 1999 Nov;24(10):1057-63. (PubMed)

Abeysinghe HR, Cedrone E, Tyan T, Xu J, Wang N. Amplification of C-MYC as the origin of the homogeneous staining region in ovarian carcinoma detected by micro-FISH Cancer Genet Cytogenet 1999 Oct 15;114(2):136-43. (PubMed)

Xu J, Fong CT, Cedrone E, Sullivan J, Wang N. Prenatal identification of de novo marker chromosomes using micro-FISH approach.Clin Genet 1998 Jun;53(6):490-6. (PubMed)

Choi C, Cho S, Horikawa I, Berchuck A, Wang N, Cedrone E, Jhung SW, Lee JB, Kerr J, Chenevix-Trench G, Kim S, Barrett JC, Koi M. Loss of heterozygosity at chromosome segment Xq25-26.1 in advanced human ovarian carcinomas. Genes Chromosomes Cancer 20(3):234-42, 1997.

Xu J, Tyan T, Cedrone E, Savaraj N, Wang N. Detection of 11q13 amplification as the origin of a homogeneously staining region in small cell lung cancer by chromosome microdissection. Genes Chromosomes Cancer 1996 Nov;17(3):172-8. (PubMed)

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