The potential male-specific oncogenic function of Cdca7l in astrocytoma

Wednesday, October 10, 2012 — Poster Session II
Noon – 2:00 p.m	Natcher Conference Center, Building 45	NCI	CANCER-20

Authors

• MH Lee
• JC Amlin-Van Schaick
• KW Broman
• KM Reilly

Abstract

The most common types of primary CNS-tumors astrocytoma are currently incurable. Astrocytoma shows male-predominance, with a male-to-female ratio of 1.31:1. Our lab has demonstrated that astrocytoma-tumorigenesis in Nf1-/+;Trp53-/+cis (NPcis)-mouse model shows gender-bias in certain genetic context. Using linkage analysis in NPcis-mouse, we have identified a male-specific genetic modifier on distal chromosome12, named Arlm1 for Astrocytoma resistance locus in males1. Arlm1 is syntenic to human Chr7p15, 7p21, 7q36, and 14q32 regions that are frequently altered in human astrocytoma-patients. Furthermore, combinational bioinformatics approaches have identified Cell division cycle-associated 7-like (Cdca7l) as a strong candidate for a male-specific susceptibility gene for astrocytoma within this Arlm1 locus. To investigate Cdca7l’s role in astrocytoma, we analyzed Cdca7l expression in human and mouse astrocytoma-cell lines in both genders. Our data showed that Cdca7l was up-regulated in astrocytoma-cells compared to normal brain with male-predominance. Furthermore, shRNA-mediated Cdca7l-depletion in male-derived mouse astrocytoma-cells led to the reduction of both cell growth and viability, suggesting its oncogenic role in astrocytoma. On the other hand, Cdca7l-overexpression in female-derived mouse astrocytoma-cells showed less degree of cell proliferation and viability increases. Further analyses in male- and female-derived astrocytoma-cells will address whether the oncogenic function of Cdca7l is indeed male-specific or male-prevalent in astrocytoma.

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