Areas of Interest
The most longstanding interest of our laboratory has been in the molecular genetic underpinnings of tumors of the endocrine glands. It was in the context of a search for a parathyroid
tumor oncogene lying adjacent to a clonal chromosomal breakpoint that we discovered cyclin D1 (PRAD1). Cyclin D1 has proven to play a key role in cell cycle regulation, and has emerged
as a major human oncogene, important in multiple types of tumors including breast cancer and B-cell lymphoma. We are currently pursuing a number of approaches, including the use of
transgenic mouse models, to learn more about the precise mechanisms by which cyclin D1 exerts its oncogenic effects. In addition to the cyclin D1 work, we are continuing a major
initiative seeking additional genes that contribute to endocrine neoplasia, and recently identified HRPT2 gene mutations as a major cause of parathyorid cancer. Furthermore, we are
interested in clarifying the link between abnormal proliferation and hormonal function, a fundamental problem in endocrine tumorigenesis, and have developed a transgenic mouse model of
hyperparathyroidism which provides an appealing system in which to pursue these questions.
Mallya SM, Gallagher JJ, Arnold A. Analysis of microsatellite instability in sporadic parathyroid adenomas. J Clin Endocrinol Metab 2003; 88:1248-1251.
Costa J, Shattuck TM, Imanishi Y, Palanisamy N, Gaz RD, Shoback D, Clark OH, Monchik JM, Wierman ME, Hollenberg A, Tojo K, Chaganti RSK, Arnold, A. Mutational analyses of connexin 26,
connexin 30 and connexin 46 as candidate tumor suppressor genes in parathyroid carcinoma. J Endocr Genet 2003; 3:57-62.
Shattuck TM, Valimaki S, Obara T, Gaz RD, Clark OH, Shoback D, Wierman ME, Tojo K, Robbins CM, Carpten JD, Farnebo LO, Larsson C, Arnold A. Somatic and germ-line mutations of the
HRPT2 gene in sporadic parathyroid carcinoma. N Engl J Med 2003 Oct 30; 349(18):1722-9.
Imanishi Y, Tahara H, Palanisamy N, Spitalny S, Salusky IB, Goodman W, Brandi ML, Drueke TB, Sarfati E, Urena P, Chaganti RSK, Arnold A. Clonal chromosomal defects in the molecular
pathogenesis of refractory hyperparathyroidism of uremia. J Amer Soc Nephrol 2002; 13:1490-1498.
Imanishi Y, Hall C, Sablosky M, Brown EM, Arnold A. New method for in vivo analysis of parathyroid hormone-calcium setpoint in mice. J Bone Miner Res 2002; 17:1656-1661.
Shattuck TM, Costa J, Bernstein M, Jensen RT, Chung DC, Arnold A. Mutational analysis of Smad3, a candidate tumor suppressor implicated in transforming growth factor-B and memin
pathways, in parathyroid adenomas and enteropancreatic endocrine tumors. J Clin Endocrinol Metab 2002; 87:3911-3914.
Imanishi Y, Hosokawa Y, Yoshimoto K, Schipani E, Mallya S, Papanikolaou A, Kifor O, Tokura T, Sablosky M, Ledgard F, Gronowicz G, Wang TC, Schmidt EV, Hall C, Brown EM, Bronson R,
Arnold A. Primary hyperparathyroidism caused by parathyroid-targeted overexpression of cyclin D1 in transgenic mice. J Clin Invest 2001; 107:1093-1102.
Hosokawa Y, Papanikolaou A, Cardiff RD, Yoshimoto K, Bernstein M, Wang TC, Schmidt EV, Arnold A. In vivo analysis of mammary and non-mammary tumorigenesis in MMTV-cyclin D1transgenic
mice deficient in p53. Transgenic Res 2001; 10:471-478.
Brown SB, Brierley TT, Palanisamy N, Salusky IB, Goodman W, Brandi ML, Drueke TB, Sarfati E, Urena P, Chaganti RSK, Pike JW, Arnold A. Vitamin D receptor as a candidate tumor
suppressor gene in severe hyperparathyroidism of uremia. J Clin Endocrinol Metab 2000; 85:868-72.