1: Gene. 2004 Apr 28;331:53-63. 

Differentiation phenotypes of pancreatic islet beta- and alpha-cells are closely
related with homeotic genes and a group of differentially expressed genes.

Mizusawa N, Hasegawa T, Ohigashi I, Tanaka-Kosugi C, Harada N, Itakura M,
Yoshimoto K.

Department of Pharmacology, School of Dentistry, The University of Tokushima,
Tokushima City, Japan.

To identify the genes that determine differentiation phenotypes, we compared
gene expression of pancreatic islet beta- and alpha-cells, which are derived
from the common precursor and secrete insulin and glucagon, respectively. The
expression levels of homeotic genes including Hox genes known to determine
region specificity in the antero-posterior (AP) body axis, tissue-specific
homeobox genes, and other 8,734 genes were compared in a beta- and alpha-cell
line of MIN6 and alpha TC1.6. The expression of homeotic genes were surveyed
with reverse transcription-polymerase chain reaction (RT-PCR) using degenerate
primers corresponding to invariant amino acid sequences within the homeodomain
and subsequently with specific primers. Expression of Hoxc6, Hoxc9, Hoxc10,
Pdx1, Cdx2, Gbx2, Pax4, and Hlxb9 genes in MIN6 was higher than those in alpha
TC1.6, while expression of Hoxa2, Hoxa3, Hoxa5, Hoxa6, Hoxa7, Hoxa9, Hoxa10,
Hoxa13, Hoxb3, Hoxb5, Hoxb6, Hoxb13, Hoxb8, and Brain4 genes in alpha TC1.6 was
higher than those in MIN6. Out of 8,734 mouse genes screened with high-density
mouse cDNA microarrays for MIN6- and alpha TC1.6-derived cDNA, 58 and 25 genes
were differentially over- and under-expressed in MIN6, respectively. GLUTag,
which is derived from a large bowel tumor and expresses the proglucagon gene,
showed a comparatively similar expression profile to that of alpha TC1.6 in both
homeotic and other genes analyzed in cDNA microarray. Our results are consistent
with the interpretation that not only the tissue-specific homeotic genes, but
also Hox genes are related to differentiation phenotypes of pancreatic beta- and
alpha-cells rather than their regional specification of the body in vertebrates.

PMID: 15094191 [PubMed - indexed for MEDLINE]


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2: Leukemia. 2002 Feb;16(2):186-95. 

Quantitative HOX expression in chromosomally defined subsets of acute
myelogenous leukemia.

Drabkin HA, Parsy C, Ferguson K, Guilhot F, Lacotte L, Roy L, Zeng C, Baron A,
Hunger SP, Varella-Garcia M, Gemmill R, Brizard F, Brizard A, Roche J.

Division of Medical Oncology, University of Colorado Health Sciences and Cancer
Centers, Denver, CO 80262, USA.

We used a degenerate RT-PCR screen and subsequent real-time quantitative RT-PCR
assays to examine the expression of HOX and TALE-family genes in 34 cases of
chromosomally defined AML for which outcome data were available. AMLs with
favorable cytogenetic features were associated with low overall HOX gene
expression whereas poor prognostic cases had high levels. Characteristically,
multiple HOXA family members including HOXA3-HOXA10 were jointly overexpressed
in conjunction with HOXB3, HOXB6, MEIS1 and PBX3. Higher levels of expression
were also observed in the FAB subtype, AML-M1. Spearmann correlation
coefficients indicated that the expression levels for many of these genes were
highly inter-related. While we did not detect any significant correlations
between HOX expression and complete response rates or age in this limited set of
patients, there was a significant correlation between event-free survival and
HOXA7 with a trend toward significance for HoxA9, HoxA4 and HoxA5. While
patients with elevated HOX expression did worse, there were notable exceptions.
Thus, although HOX overexpression and clinical resistance to chemotherapy often
coincide, they are not inextricably linked. Our results indicate that
quantitative HOX analysis has the potential to add new information to the
management of patients with AML, especially where characteristic chromosomal
alterations are lacking.

PMID: 11840284 [PubMed - indexed for MEDLINE]


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