PTHrP increases xenograft growth and promotes integrin alpha6beta4 expression and Akt activation in colon cancer.

Abstract	Parathyroid hormone-related protein (PTHrP) is expressed by human colon cancer tissue and cell lines. Expression of PTHrP and phosphatidylinositol 3-kinase (PI3-K) pathway components correlates with the severity of colon carcinoma. Here we observed a positive effect of endogenous PTHrP on LoVo (human colon cancer) cell proliferation, migration, invasion, integrin alpha6 and beta4 expression, and p-Akt levels. There was a direct correlation between PTHrP expression and anchorage-independent cell growth. PTHrP significantly increased xenograft growth; tumors from PTHrP-overexpressing cells showed increased expression of integrins alpha6 and beta4, and PI3-K pathway components. The higher expression of PTHrP in human colon cancer adenocarcinoma vs. normal colonic mucosa was accompanied by increased integrin alpha6 and beta4 levels. Elevated PTHrP expression in colon cancer may thus upregulate integrin alpha6beta4 expression, with consequent PI3-K activation. Targeting PTHrP might result in effective inhibition of tumor growth, migration, and invasion.
Authors	Xiaoli Shen, Piotr G Rychahou, B Mark Evers, Miriam Falzon
Journal	Cancer letters (Cancer Lett) Vol. 258 Issue 2 Pg. 241-52 (Dec 18 2007) ISSN: 0304-3835 [Print] Ireland
PMID	17964713 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References	Integrin alpha6beta4 Parathyroid Hormone-Related Protein RNA, Small Interfering Proto-Oncogene Proteins c-akt
Topics	Animals Cell Line, Tumor Cell Movement (genetics, physiology) Cell Proliferation Colonic Neoplasms (genetics, metabolism, pathology) Humans Immunohistochemistry Integrin alpha6beta4 (biosynthesis) Male Mice Mice, Nude Neoplasm Invasiveness Neoplasms, Experimental (genetics, metabolism, pathology) Parathyroid Hormone-Related Protein (genetics, physiology) Proto-Oncogene Proteins c-akt (metabolism) RNA, Small Interfering (genetics) Transfection Transplantation, Heterologous Tumor Burden

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