This Article Full Text Full Text (PDF) Correction (v69,p8832) Correction (v69,p8832) All Versions of this Article: 0008-5472.CAN-09-0194v1 69/18/7473    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Fleming, N. I. Articles by Thomas, D. M. PubMed PubMed Citation Articles by Fleming, N. I. Articles by Thomas, D. M.

Parathyroid Hormone–Related Protein Protects against Mammary Tumor Emergence and Is Associated with Monocyte Infiltration in Ductal Carcinoma In situ

¹ Research Division and ² Department of Anatomical Pathology, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia and Departments of ³ Pathology and ⁴ Medicine, St. Vincent's Hospital, Fitzroy, Victoria, Australia

Requests for reprints: David M. Thomas, Research Division, Peter MacCallum Cancer Centre, Locked Bag 1, A'Beckett Street, Melbourne, Victoria 8006, Australia. Phone: 61-396561238; Fax: 61-395946125; E-mail: david.thomas{at}petermac.org.

Key Words: PTHrP • monocyte • HER-2/neu • breast cancer • DCIS

Parathyroid hormone–related protein (PTHrP) is required for mammary gland development and promotes the growth of breast cancer metastases within bone. However, there are conflicting reports of the prognostic significance of its expression in primary breast cancers. To study the role of PTHrP in early breast cancer, the effect of conditional deletion of PTHrP was examined in the context of neu-induced mammary tumorigenesis. Loss of PTHrP resulted in a higher tumor incidence. Transcriptional profiling of the tumors revealed that PTHrP influenced genes relevant to heterotypic cell signaling, including regulators of monocyte recruitment. Immunohistochemical analysis of human breast cancers revealed that PTHrP expression was associated with both HER-2/neu expression and macrophage infiltration in preinvasive ductal carcinoma in situ. The gene expression signature associated with loss of PTHrP expression in vivo correlated with poorer outcome in human breast cancer. Together, these data indicate that loss of PTHrP accelerates mammary tumorigenesis possibly by a non–cell-autonomous tumor suppressor pathway. [Cancer Res 2009;69(18):7473–9]

This article has been cited by other articles:

				Correction: Parathyroid Hormone-Related Protein Protects against Mammary Tumor Emergence and Is Associated with Monocyte Infiltration in Ductal Carcinoma In situ Cancer Res., November 15, 2009; 69(22): 8832 - 8832. [Full Text] [PDF]