Role of Arsenic and cadmium in the development of bladder cancer:
My Lab is interested in studying the role of arsenic and cadmium in the development of bladder cancer. Previously it was unknown if either cadmium (Cd+2) or arsenite (As+3) could directly cause the malignant transformation of human urothelial cells. In my lab, we have been able to directly transform the non-tumorigenic urothelial cell line UROtsa, by exposing them long term in vitro to Cd+2 and As+3. The histology of the tumor heterotransplants produced by UROtsa cells malignantly transformed by Cd+2 and As+3 had epithelial features consistent with those of a classic transitional-cell carcinoma (TCC) of the bladder. However, a unique feature of these tumors were the presence of areas that showed prominent squamous differentiation. Of particular interest was the expression of the protein, keratin 6 which was restricted to the areas of the tumors that displayed some squamous features. In fact, keratin 6 immunoreactivity allowed one to focus on, and more easily identify, areas in the tumors having features of squamous differentiation. This suggests that keratin 6 could not only be a potential biomarker for metal exposure but it could also identify areas in a tumor that may eventually display prominent squamous diffentiation. In the United States and Europe, TCC’s that contain a prominent squamous component are rare; however, there is some evidence that the presence of a squamous component within transitional cell carcinomas may indicate a poor prognosis for the patient. Furthermore, we have recently shown that the expression of keratin 6 is regulated by the activation of the ERK1/2 pathway.
- Slusser-Nore, Garrett SH, Zhou XD, Sens DA, Sens MA, Somji S. The expression of keratin 6 is regulated by the activation of the ERK1/2 pathway in arsenite transformed UROtsa cells. Toxicol Appl Pharmacol. 2017 May 10. pii: S0041-008X(17)30201-6.
- Shrestha S, Somji S, Sens DA, Slusser-Nore, Patel DH, Savage E, Garrett SH. Human renal tubular cells contain CD24/CD133 progenitor cell population: Implications for tubular regeneration after toxicant induced damage using cadmium as a model. Toxicol Appl Pharmacol. 2017 Sep 15;331:116-129.
- Voels, B, Wang L, Sens DA, Garrett SH, Zhang Ke, Somji S. The unique C- and N-terminal sequences of metallothionein isoform 3 mediate growth inhibition and vectorial active transport in MCF-7 cells. BMC Cancer. 2017 Sep 15:331:116-129.
- Voels B, Zhang R, Wang L, Garrett SH, Sens DA, Dunlevy JR, Zhou XD, Somji S. Elevated connexin 43 expression in arsenite-and cadmium-transformed human bladder cancer cells, tumor transplants and selected high grade human bladder cancers. Exp Toxicol Pathol. 2016 Oct;68(9):479-491. doi: 10.1016/j.etp.2016.08.003. Epub 2016 Aug 13.
- Sandquist EJ, Somji S, Dunlevy JR, Garrett SH, Zhou XD, Slusser-Nore A, Sens DA. Loss of N-Cadherin Expression in Tumor Transplants Produced From As+3- and Cd+2-Transformed Human Urothelial (UROtsa) Cell Lines. PLoS One. 2016 May 25;11(5):e0156310. doi: 10.1371/journal.pone.0156310. eCollection 2016.
- Slusser-Nore A, Larson-Casey JL, Zhang R, Zhou XD, Somji S, Garrett SH, Sens DA, Dunlevy JR. SPARC Expression Is Selectively Suppressed in Tumor Initiating Urospheres Isolated from As+3- and Cd+2-Transformed Human Urothelial Cells (UROtsa) Stably Transfected with SPARC. PLoS One. 2016 Jan 19;11(1):e0147362. doi: 10.1371/journal.pone.0147362. eCollection 2016.
- Slusser A, Bathula CS, Sens DA, Somji S, Sens MA, Zhou XD, Garrett SH. Cadherin expression, vectorial active transport, and metallothionein isoform 3 mediated EMT/MET responses in cultured primary and immortalized human proximal tubule cells. PLoS One. 2015 Mar 24;10(3):e0120132. doi: 10.1371/journal.pone.0120132. eCollection 2015.
- Slusser A, Zheng Y, Zhou XD, Somji S, Sens DA, Sens MA, Garrett SH. Metallothionein isoform 3 expression in human skin, related cancers and human skin derived cell cultures. Toxicol Lett. 2015 Jan 5;232(1):141-8. doi: 10.1016/j.toxlet.2014.09.028. Epub 2014 Oct 5.
- 9. Mehus AA, Muhonen WW, Garrett SH, Somji S, Sens DA, Shabb JB. Quantitation of human metallothionein isoforms: a family of small, highly conserved, cysteine-rich proteins. Mol Cell Proteomics. 2014 Apr;13(4):1020-33. doi: 10.1074/mcp.M113.033373. Epub 2014 Feb 3
Complete list of Published work in MyBibliography:
1986 BSc. St. Josephs College, Karachi, Pakistan
1989 MSc. University of Karachi, Pakistan (Microbiology)
1996 Ph.D. The George Washington University, Washington DC (Microbiology & Immunology)