Oct4 expression in adult human stem cells: evidence in support of the stem cell theory of carcinogenesis

Abstract

The Oct3/4 gene, a POU family transcription factor, has been noted as being specifically expressed in embryonic stem cells and in tumor cells but not in cells of differentiated tissues. With the ability to isolate adult human stem cells it became possible to test for the expression of Oct3/4 gene in adult stem cells and to test the stem cell theory of carcinogenesis. Using antibodies and PCR primers we tested human breast, liver, pancreas, kidney, mesenchyme and gastric stem cells, the cancer cell lines HeLa and MCF-7 and human, dog and rat tumors for Oct4 expression. The results indicate that adult human stem cells, immortalized non-tumorigenic cells and tumor cells and cell lines, but not differentiated cells, express Oct4. Oct4 is expressed in a few cells found in the basal layer of human skin epidermis. The data demonstrate that adult stem cells maintain expression of Oct4, consistent with the stem cell hypothesis of carcinogenesis.

Highly purified CD44+ prostate cancer cells from xenograft human tumors are enriched in tumorigenic and metastatic progenitor cells

“…Second, the CD44 þ PCa cells acutely purified from xenograft tumors express higher mRNA levels of several 'stemness' genes, including Oct-3/4, Bmi, b-catenin, and SMO. Oct-3/4 is a transcription factor critical for the self-renewal of teratocarcinoma cells and embryonic SCs (Chambers and Smith, 2004) and is also expressed in some stem-like cancer cells (Tai et al, 2005). Bmi plays an essential role in determining the self-renewal and long-term proliferative capacity of not only normal hematopoietic and CD44 þ cell population enriched in prostate tumor progenitors L Patrawala et al neural SCs but also leukemic SCs (Valk-Lingbeek et al, 2004).…”

Comparative Analysis of Oct4 in Different Histological Subtypes of Esophageal Squamous Cell Carcinomas in Different Clinical Conditions

“…This group also observed uneven distribution of Oct4 positive cells within tumor, ranging from few scattered individual cells to cells in large aggregates. There are two studies (Tai et al, 2005;He et al, 2012) who had reported Oct4 expression by dysplastic and hyperplastic esophageal mucosa confining to the proliferative zone, and not expressed by the normal mucosa. Oct4 positivity is reported in certain adult tissue including benign endometrial stromal cells (Atlasi et al, 2006;Cauffman et al, 2006;Mathai et al, 2006;Katona et al, 2007;Zangrossi et al, 2007;Atlasi et al, 2008;Forte et al, 2009).…”

The role of oxygen availability in embryonic development and stem cell function

“…Oct4 expression is tightly controlled during embryogenesis and adult life: Oct4 downregulation is required for differentiation of the trophectoderm lineage and subsequent gastrulation by the epiblast; however, Oct4 expression is maintained in PGCs. In the adult, Oct4 is exclusively expressed in germ cells, and had been detected in stem-cell populations such as bone marrow multipotent adult progenitors, haematopoietic stem cells, and stem cells that reside in epidermal basal layers 78,79 . More recent studies demonstrate that OCT4 is essential for germ-cell maintenance, but dispensable for somatic stem-cell self-renewal 80,81 .…”