Structural Characterization of Three Novel Rat OKL38 Transcripts, Their Tissue Distributions, and Their Regulation by Human Chorionic Gonadotropin

Abstract

We 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 eight 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 in the rat mammary gland and ovary. Importantly, overexpression of RtOKL38-enhanced green fluorescence protein 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 human chorionic gonadotropin protection against mammary carcinogenesis, and the availability of the three rat OKL38 cDNAs may help to elucidate the possible role of OKL38 in cellular growth, differentiation, and carcinogenesis.

Histone Arg Modifications and p53 Regulate the Expression of OKL38, a Mediator of Apoptosis

“…OKL38 Overexpression Leads to Apoptosis in U2OS Cells-The expression of OKL38 has been found to be repressed in 60 -70% of human kidney and liver cancers (34,35). Consistent with the idea that the loss of OKL38 expression is beneficial to cancer cell growth (27,30), we found that the endogenous OKL38 protein in U2OS cells and MCF-7 cells was hard to detect (Fig.…”

“…Previous studies have found that the overexpression of OKL38 induced cell death in A498 (kidney cancer), buffalo rat liver, and MCF-7 (breast cancer) cells (27,34,35). However, the mechanisms by which OKL38 overexpression induced apoptosis remained unclear.…”

OKL38 is an oxidative stress response gene stimulated by oxidized phospholipids

“…Its expression was lost or reduced in tumor cell lines and tumor tissues (10,11). The only study on OKL38 regulation showed that administration of human chorionic gondotropin to rats stimulated the expression of OKL38 in mammary gland and ovary but not in other tissues (12). However, little is known about the mechanism of OKL38 regulation and its molecular function.…”

RNA sequencing supports distinct reactive oxygen species-mediated pathways of apoptosis by high and low size mass fractions of Bay leaf (Lauris nobilis) in HT-29 cells

“…77 OSGIN1 regulates the differentiation and proliferation of cells, and its over-expression induces apoptosis and cell death, as shown in A498 (malignant kidney cells), buffalo rat liver, and MCF-7 (malignant breast cells). [78][79][80] Loss of OSGIN1 is positively correlated with rapid tumor growth and metastasis. 81 Conversely, its upregulation by bay leaf, particularly by LFBL (Table 2), likely contributed to induction of HT-29 apoptosis and cell death.…”