TY - JOUR
T1 - A vasoactive intestinal peptide receptor analog alters the expression of homeobox genes
AU - Steingart, Ruth A.
AU - Heldenberg, Eitan
AU - Pinhasov, Albert
AU - Brenneman, Douglas E.
AU - Fridkin, Mati
AU - Gozes, Illana
PY - 2002/10/11
Y1 - 2002/10/11
N2 - A lipophilic analog of vasoactive intestinal peptide (VIP), stearyl-Nle17-neurotensin6-11VIP7-28 (SNH), that inhibited lung cancer growth, has been previously described. The mechanism of SNH inhibition of cancer growth is still being elucidated. The present study examined the effects of SNH on homeobox genes in the colon cancer cell line HT 29 that expresses VIP receptors. Homeobox genes contain a characteristic DNA sequence, coding for a stretch of 61 amino acid homeodomain that binds specific DNA motifs. While the HOX gene family contains a single homeodomain, the POU gene family contains an additional DNA binding homeodomain. HT 29 cells were incubated with SNH; RNA was extracted and subjected to reverse-transcription-polymerase chain reaction (RT-PCR) with primers that matched the conserved area of the various HOX or POU genes. The PCR products that were altered by SNH treatment were sequenced. Three candidate SNH-responsive genes, the HOX A4, the HOX B5 and the PUO V transcription factor I (Oct-3) were identified. Semi-quantitative RT-PCR with specific primers confirmed the increase in HOX A4 and the decrease in Oct-3 expression levels following SNH treatment. Thus, the HOX A4 and the Oct-3 homeobox genes may partially mediate SNH activity on cancer cells.
AB - A lipophilic analog of vasoactive intestinal peptide (VIP), stearyl-Nle17-neurotensin6-11VIP7-28 (SNH), that inhibited lung cancer growth, has been previously described. The mechanism of SNH inhibition of cancer growth is still being elucidated. The present study examined the effects of SNH on homeobox genes in the colon cancer cell line HT 29 that expresses VIP receptors. Homeobox genes contain a characteristic DNA sequence, coding for a stretch of 61 amino acid homeodomain that binds specific DNA motifs. While the HOX gene family contains a single homeodomain, the POU gene family contains an additional DNA binding homeodomain. HT 29 cells were incubated with SNH; RNA was extracted and subjected to reverse-transcription-polymerase chain reaction (RT-PCR) with primers that matched the conserved area of the various HOX or POU genes. The PCR products that were altered by SNH treatment were sequenced. Three candidate SNH-responsive genes, the HOX A4, the HOX B5 and the PUO V transcription factor I (Oct-3) were identified. Semi-quantitative RT-PCR with specific primers confirmed the increase in HOX A4 and the decrease in Oct-3 expression levels following SNH treatment. Thus, the HOX A4 and the Oct-3 homeobox genes may partially mediate SNH activity on cancer cells.
KW - HT 29 cell line
KW - Homeobox genes
KW - Stearyl-Nle-neurotensinVIP (SNH)
KW - Vasoactive intestinal peptide (VIP)
UR - http://www.scopus.com/inward/record.url?scp=0037063712&partnerID=8YFLogxK
U2 - 10.1016/S0024-3205(02)02082-9
DO - 10.1016/S0024-3205(02)02082-9
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C2 - 12270759
AN - SCOPUS:0037063712
SN - 0024-3205
VL - 71
SP - 2543
EP - 2552
JO - Life Sciences
JF - Life Sciences
IS - 21
ER -