Huynh et al. (2001) found that onset and advancement of pregnancy in rat was associated with an increase in Okl38 gene expression. In situ hybridization detected Okl38 in undifferentiated mammary epithelial cells of nonpregnant rats, and expression was upregulated in secretory epithelial of 18-day pregnant rats. Northern blot analysis detected reduced OKL38 expression in human breast cancer cell lines compared with normal mammary tissue. Expression was also reduced in chemically-induced rat mammary tumors. Overexpression of OKL38 in a human breast cancer cell line reduced the ability of these cells to form tumors in nude mice.
NCBI Summary:
This gene encodes an oxidative stress response protein that regulates cell death. Expression of the gene is regulated by p53 and is induced by DNA damage. The protein regulates apoptosis by inducing cytochrome c release from mitochondria. It also appears to be a key regulator of both inflammatory and anti-inflammatory molecules. The loss of this protein correlates with uncontrolled cell growth and tumor formation. Naturally occurring read-through transcription exists between this gene and the neighboring upstream malonyl-CoA decarboxylase (MLYCD) gene, but the read-through transcripts are unlikely to produce a protein product. [provided by RefSeq, Aug 2011]
Structural Characterization of three Novel Rat OKL38 transcripts, their tissue distributions, and their regulation by human chorionic gonadotropin.
Ong CK, Young Ng C, Leong C, Ng CP, et al previously identified a novel pregnancy-induced growth inhibitory gene, OKL38. To develop a rat model for further characterization of OKL38's role in the initiation and progression of breast and ovarian cancer, we now report the cloning and characterization of three novel rat OKL38 cDNAs that are derived through alternative splicing and differential promoter usage. These three transcripts differ in their 5' untranslated regions but share a common open reading frame that encoded for a 52 kDa protein. OKL38 is mapped to chromosome 19 spanning a region of approximately 15 kb and contains 8 exons. Differential expression of these three rat OKL38 transcripts was observed in liver, kidney, ovary, mammary gland and uterus. In situ hybridization localized the rat OKL38 transcripts to the luminal epithelial cells of the rat mammary gland and to the granulosa cells in the rat ovary. In vivo studies showed that the RtOKL38-2.0 transcript and protein were regulated by human chorionic gonadotropin (hCG) in the rat mammary gland and ovary. Importantly, over-expression of RtOKL38-eGFP fusion protein in Buffalo Rat Liver cells resulted in growth inhibition and cell death. Our present findings suggest that OKL38 may function as an effector for hCG-protection against mammary carcinogenesis and the availability of the three rat OKL38 cDNAs may help to elucidate its possible role in cellular growth, differentiation and carcinogenesis.