Disease relevance of GRHL1

• Human LBP-32/MGR is a Repressor of the P450scc in Human Choriocarcinoma Cell Line JEG-3 [1].
• We have reported that a 32-kDa laminin-binding protein (LBP-32) was overexpressed in colorectal cancer at the messenger RNA (mRNA) level and correlated with clinical staging [2].
• These findings suggest a role for LBP-32 in colon cancer progression and metastasis.(ABSTRACT TRUNCATED AT 250 WORDS)[2]
• More importantly, the LBP-32 mRNA was expressed more highly in the invasive lesions of the cancer and liver metastases compared with the cancer lesions in situ [3].

High impact information on GRHL1

• In addition, there were significant qualitative and quantitative differences between NH32 and TK6 with respect to UV mutagenesis at the endogenous hypoxanthine phosphoribosyltransferase (hprt) locus [4].
• Following irradiation with UV (either monochromatic 254 nm UV or broad-spectrum simulated sunlight), relative to wild-type TK6, p53-null NH32 exhibited virtually identical clonogenic survival and kinetics of G1-S progression but was nonetheless profoundly resistant to apoptosis [4].
• However, important disparities were observed between genetically p53-deficient NH32 and E6-expressing TK6-5E regarding the manner in which they responded to UV-induced genotoxic stress in relation to wild-type TK6 [4].
• The shortest telomeres were found in WTK1- and NH32-derived cells, and these cells had 5- to 10-fold higher levels of chromosome instability [5].
• A novel delivery system was used to study NO-mediated cyto- and genotoxicity in two human lymphoblastoid cell lines, TK6 (wild-type p53) and NH32 (p53-null but isogenic to TK6) [6].

Biological context of GRHL1

• Using radiation hybrid mapping, we identified LBP-32/MGR on human chromosome 2p25 [1].
• Luciferase reporter gene assays showed that LBP-32/MGR specifically repressed transcriptional activation of the human P450scc promoter [1].
• Despite their extensive sequence homology, Grhl1 and Grhl2 are unable to compensate for loss of Grhl3 in these developmental processes [7].
• These findings expand our understanding of the unique role of Grhl3 in neurulation and epidermal morphogenesis, and provide a focus for further functional analysis of the Grhl genes during mouse embryogenesis [7].
• The degree of constitutive H2AX phosphorylation was distinctly lower in NH32, WTK1 and HL-60 compared to TK6 cells in all phases of the cell cycle [8].

Anatomical context of GRHL1

• The peak (PGR) and mean (MGR) gliding resistance of the middle finger flexor digitorum superficialis tendon were measured with the wrist in 0, 30, and 60 degrees of flexion and extension [9].
• In this study, we have analyzed the role of LBP-32 in tumor cell attachment and invasion through various basement membrane components [2].
• The results showed that LBP-32 mRNA was expressed at a low level in the normal colonic mucosa adjacent to the tumor compared with colon cancer tissues [3].
• Interferons upregulate the expression of laminin and its receptor LBP-32 in cultured cells [10].

Associations of GRHL1 with chemical compounds

• Because placental P450scc expression is essential for pregnancy and steroid biosynthesis, the placental expression and transcriptional repressor activity of LBP-32/MGR in JEG-3 cells suggest it has a role as a transcriptional modulator of steroid biosynthesis [1].
• Also, the degree of attenuation of constitutive H2AX phosphorylation by N-acetyl-L-cysteine was less pronounced in NH32, WTK1, and HL-60, compared to TK6 cells [8].
• In the present study, we provide evidence that growth of cells from three human lymphoblastoid cell lines TK6, NH32 and WTK1 in the presence of the glucose antimetabolite 2-deoxy-D-glucose (2-DG) led to a distinct reduction in the level of CHP [11].

Other interactions of GRHL1

• We studied immunohistological and biochemical aspects of the CD44 molecule with a mAb produced in our lab: GRHL-1 [12].
• The results showed that (a) laminin and collagen IV (but not fibronectin) play a role in colon cancer cell attachment to substrata, and (b) anti-sense RNA of LBP-32 inhibits tumor cell attachment and invasiveness in vitro [2].

Analytical, diagnostic and therapeutic context of GRHL1

• Using a Northern blot, we found that LBP-32/MGR mRNA was expressed mainly in the human placenta [1].
• In order to overcome these problems, we examined the LBP-32 mRNA expression in colorectal carcinomas by in situ hybridization [3].

References