Transactivation of the PTHrP gene in squamous carcinomas predicts the occurrence of hypercalcemia in athymic mice

John J. Wysolmerski, Rupangi Vasavada, John Foley, Eleanor C. Weir, William J. Burtis, Subhash C. Kukreja, Theresa A. Guise, Arthur E. Broadus, William M. Philbrick

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Humoral hypercalcemia of malignancy (HHM) is caused by the secretion of parathyroid hormone-related protein (PTHrP) by tumor cells, and tumors of squamous histology are the ones most commonly complicated by HHM. To determine why some squamous tumors cause HHM and others do not, we quantitated the levels of PTHrP mRNA expression and PTHrP secretion in a series of eight squamous tumor lines. As anticipated, we found that the level of PTHrP mRNA expression in individual lines correlated with their PTHrP secretion rates. However, PTHrP mRNA levels varied widely in individual lines, and only those tumor lines with the highest levels of PTHrP gene expression were able to cause hypercalcemia in athymic mice. We found that a specific segment of the PTHrP promoter could reproduce the relative pattern of PTHrP gene expression when cloned in front of a chloramphenicol acetyltransferase reporter gene and transiently transfected into these squamous lines. Deletional analysis confirmed that specific sequences within the PTHrP gene promoter appeared to be involved in the transactivation of the gene in tumor lines expressing high levels of PTHrP mRNA. These data suggest that the ability of a given squamous tumor to cause HHM is ultimately a function of its level of PTHrP gene expression, which in turn appears to be a function of the ability of specific transcription factors to transactivate PTHrP gene expression.

Original languageEnglish (US)
Pages (from-to)1043-1049
Number of pages7
JournalCancer Research
Volume56
Issue number5
StatePublished - Mar 1 1996

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Parathyroid Hormone-Related Protein
Hypercalcemia
Nude Mice
Transcriptional Activation
Squamous Cell Carcinoma
Genes
Neoplasms
Gene Expression
Messenger RNA
Chloramphenicol O-Acetyltransferase
Reporter Genes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Wysolmerski, J. J., Vasavada, R., Foley, J., Weir, E. C., Burtis, W. J., Kukreja, S. C., ... Philbrick, W. M. (1996). Transactivation of the PTHrP gene in squamous carcinomas predicts the occurrence of hypercalcemia in athymic mice. Cancer Research, 56(5), 1043-1049.

Transactivation of the PTHrP gene in squamous carcinomas predicts the occurrence of hypercalcemia in athymic mice. / Wysolmerski, John J.; Vasavada, Rupangi; Foley, John; Weir, Eleanor C.; Burtis, William J.; Kukreja, Subhash C.; Guise, Theresa A.; Broadus, Arthur E.; Philbrick, William M.

In: Cancer Research, Vol. 56, No. 5, 01.03.1996, p. 1043-1049.

Research output: Contribution to journalArticle

Wysolmerski, JJ, Vasavada, R, Foley, J, Weir, EC, Burtis, WJ, Kukreja, SC, Guise, TA, Broadus, AE & Philbrick, WM 1996, 'Transactivation of the PTHrP gene in squamous carcinomas predicts the occurrence of hypercalcemia in athymic mice', Cancer Research, vol. 56, no. 5, pp. 1043-1049.
Wysolmerski JJ, Vasavada R, Foley J, Weir EC, Burtis WJ, Kukreja SC et al. Transactivation of the PTHrP gene in squamous carcinomas predicts the occurrence of hypercalcemia in athymic mice. Cancer Research. 1996 Mar 1;56(5):1043-1049.
Wysolmerski, John J. ; Vasavada, Rupangi ; Foley, John ; Weir, Eleanor C. ; Burtis, William J. ; Kukreja, Subhash C. ; Guise, Theresa A. ; Broadus, Arthur E. ; Philbrick, William M. / Transactivation of the PTHrP gene in squamous carcinomas predicts the occurrence of hypercalcemia in athymic mice. In: Cancer Research. 1996 ; Vol. 56, No. 5. pp. 1043-1049.
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