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Dianne R. Soprano, PhD

Professor, Biochemistry

Professor, Fels Institute for Cancer Research and Molecular Biology

Associate Dean, Graduate and MD/PhD Program

Telephone:  215-707-3266

Fax:  215-707-7536

Email: dsoprano@temple.edu

Department of Biochemistry

Fels Institute for Cancer Research and Molecular Biology

PhD,  Rutgers University

 

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Research in Dr. Soprano's laboratory focuses on the mechanism of action of retinoic acid (RA) at the molecular level. RA exerts its action by the transcriptional regulation of specific genes via a family of nuclear receptors called retinoic acid receptors, RARs, and retinoid X receptors, RXRs. Three distinct but highly homologous RAR isotypes have been described termed RARa, RARb and RARg. In addition, several isoforms of each RAR isotype, which vary in both the length and amino acid sequence of the N-terminal A domain, have been identified. Specifically, we are interested in the structure, function and regulation of RARs particularly during development and in tumors. First, microarray analysis and differential display have identified several mRNAs whose level of expression is altered by RA treatment in developing mouse limbs. Two of these genes are PBX and MEIS. We are currently addressing the role of the RA-dependent elevation of expression of these two genes in the differentiation of P19 embryonal carcinoma cells. These studies are aimed at the elucidation of the sequence of events involved in RA-mediating differentiation of pluripotent embryonal carcinoma cells to endodermal and neuronal cells. Second, little is known about the functional importance of the unique A/B domains associated with each of the isoforms of the three RAR isotypes. Yeast 2-hybrid screening has resulted in the identification of several unique cDNAs that encode proteins that interact with the amino terminal A/B domain of RARs. The role of these proteins in the regulation of RA-dependent gene expression is being explored with the goal of further understanding the functional importance of the A/B domains of RARs. Third, RA can inhibit the growth of many tumor cells including the CAOV3 ovarian tumor cell line. In addition, several synthetic retinoids induce apoptosis in ovarian tumor cells. Studies are currently underway examining the steps in the apoptotic pathway induced by several synthetic retinoids and the mechanism of regulation of the protein levels of the tumor suppressor gene, Rb2, during RA-induced growth inhibition of these cells. Elucidation of the mechanism of action underlying RA-dependent inhibition of tumor cell growth may lead to the development of unique retinoid treatments for cancer chemotherapy and chemoprevention. 

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Recent Medically Related Publications, Obtained from PubMed (Click on PubMed ID to view abstract)

19502054. Sun W, Carroll PJ, Soprano DR, Canney DJ, Identification of a chromone-based retinoid containing a polyolefinic side chain via facile synthetic routes. Bioorg Med Chem Lett 19:15(4339-42)2009 Aug 1

19350571. Zhao J, Zhang Z, Vucetic Z, Soprano KJ, Soprano DR, HACE1: A novel repressor of RAR transcriptional activity. J Cell Biochem 107:3(482-93)2009 Jun 1

18615582. Radu M, Soprano DR, Soprano KJ, S10 phosphorylation of p27 mediates atRA induced growth arrest in ovarian carcinoma cell lines. J Cell Physiol 217:2(558-68)2008 Nov

18446820. Fields AL, Soprano DR, Soprano KJ, Characterization of alterations of Rb2/p130 tumor suppressor in all-trans-retinoic acid resistant SK-OV3 ovarian carcinoma cells. J Cell Physiol 217:1(77-85)2008 Oct

18250153. Vucetic Z, Zhang Z, Zhao J, Wang F, Soprano KJ, Soprano DR, Acinus-S' represses retinoic acid receptor (RAR)-regulated gene expression through interaction with the B domains of RARs. Mol Cell Biol 28:8(2549-58)2008 Apr

17909034. Ravikumar S, Perez-Liz G, Del Vale L, Soprano DR, Soprano KJ, Insulin receptor substrate-1 is an important mediator of ovarian cancer cell growth suppression by all-trans retinoic acid. Cancer Res 67:19(9266-75)2007 Oct 1

17902161. Fields AL, Soprano DR, Soprano KJ, Retinoids in biological control and cancer. J Cell Biochem 102:4(886-98)2007 Nov 1

17474084. Jiang T, Soprano DR, Soprano KJ, GADD45A is a mediator of CD437 induced apoptosis in ovarian carcinoma cells. J Cell Physiol 212:3(771-9)2007 Sep

17368312. Soprano DR, Teets BW, Soprano KJ, Role of retinoic acid in the differentiation of embryonal carcinoma and embryonic stem cells. Vitam Horm 75:(69-95)2007

17073551. Buletic Z, Soprano KJ, Soprano DR, Retinoid targets for the treatment of cancer. Crit Rev Eukaryot Gene Expr 16:3(193-210)2006

16936753. Soprano KJ, Purev E, Vuocolo S, Soprano DR, Rb2/p130 and protein phosphatase 2A: key mediators of ovarian carcinoma cell growth suppression by all-trans retinoic acid. Oncogene 25:38(5315-25)2006 Aug 28

16206244. Purev E, Giordano A, Soprano DR, Soprano KJ, Interaction of PP2A catalytic subunit with Rb2/p130 is required for all-trans retinoic acid suppression of ovarian carcinoma cell growth. J Cell Physiol 206:2(495-502)2006 Feb

16052510. Ramírez CJ, Haberbusch JM, Soprano DR, Soprano KJ, Retinoic acid induced repression of AP-1 activity is mediated by protein phosphatase 2A in ovarian carcinoma cells. J Cell Biochem 96:1(170-82)2005 Sep 1

15354417. Purev E, Soprano DR, Soprano KJ, Effect of all-trans retinoic acid on telomerase activity in ovarian cancer cells. J Exp Clin Cancer Res 23:2(309-16)2004 Jun

15189119. Soprano DR, Qin P, Soprano KJ, Retinoic acid receptors and cancers. Annu Rev Nutr 24:(201-21)2004

15131049. D'Andrilli G, Masciullo V, Bagella L, Tonini T, Minimo C, Zannoni GF, Giuntoli RL 2nd, Carlson JA Jr, Soprano DR, Soprano KJ, Scambia G, Giordano A, Frequent loss of pRb2/p130 in human ovarian carcinoma. Clin Cancer Res 10:9(3098-103)2004 May 1

15095411. Qin P, Haberbusch JM, Soprano KJ, Soprano DR, Retinoic acid regulates the expression of PBX1, PBX2, and PBX3 in P19 cells both transcriptionally and post-translationally. J Cell Biochem 92:1(147-63)2004 May 1

15095280. Holmes WF, Soprano DR, Soprano KJ, Synthetic retinoids as inducers of apoptosis in ovarian carcinoma cell lines. J Cell Physiol 199:3(317-29)2004 Jun

15040006. Vuocolo S, Soprano DR, Soprano KJ, p27/Kip1 mediates retinoic acid-induced suppression of ovarian carcinoma cell growth. J Cell Physiol 199:2(237-43)2004 May

14742427. Qin P, Haberbusch JM, Zhang Z, Soprano KJ, Soprano DR, Pre-B cell leukemia transcription factor (PBX) proteins are important mediators for retinoic acid-dependent endodermal and neuronal differentiation of mouse embryonal carcinoma P19 cells. J Biol Chem 279:16(16263-71)2004 Apr 16

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