*3.1.3. ALDH1A3*

ALDH1A3 is a cytosolic homodimer that participates in RA synthesis, oxidizes both all*trans*-retinal and 9-*cis*-retinal (*K*m 0.2 μM for all-*trans*-retinal) to RA, and has an important role in embryonic development; including brain, retina, skeletal muscle, tooth buds, intestine, kidney, prostate, lung, liver and pancreas, it is expressed in various late-stage embryonic and adult rodent tissues. In humans, ALDH1A3 expression has been noted in stomach, salivary gland, breast, kidney and fetal nasal mucosa. *Aldh1a3*−/− mouse embryos die as a result of defects in nasal development.

It's been shown that ALDH1A3 takes part in the development of the eye, nucleus accumbens and olfactory bulbs, the forebrain, hair follicles and the cerebral cortex.

Aldehyde Dehydrogenase: Cancer and Stem Cells 13

ALDH7A1 is notably and differentially expressed within the first and second meiotic stages of porcine oocyte development. Screening of the promoter region *sbALDH7A1* has

Adenocarcinoma is an epithelium cancer that is generated from glandular tissue. Epithelial tissue includes, but is not limited to, the surface layer of skin, glands and a variety of other tissues that line the cavities and organs of the body. Epithelium can be derived from the three germ layers ectoderm, mesoderm and endoderm during embryologic period. Adenocarcinoma classification depends on not only being a part of the gland, but also depends on having the same secretory characteristics. But, this form of carcinoma can occur

Adenocarcinomas can arise in many tissues of the body due to the ubiquitous nature of glands within the body. While each gland may not be secreting the same substance, as long as there is an exocrine function to the cell, it is considered glandular and its malignant form is therefore named adenocarcinoma. Endocrine gland tumors, such as a VIPoma, an insulinoma, a pheochromocytoma, etc. are typically not referred to as adenocarcinomas, but rather, are often called neuroendocrine tumors. If the glandular tissue is abnormal, but benign, it is called an adenoma. Benign adenomas typically do not invade other tissues and rarely metastasize, whereas malignant adenocarcinomas do both. Colon, urogenital (cervical (Tewari*, et al.*, 2002), prostate, urachus and vagina), breast (Buchholz, 2009), esophagus, pancreas, stomach and throat are several examples of adenocarcinoma (Subramanian &

It is reported that ALDH expression marks pancreatic cancer stem cells. Also, they have mentioned that the enhanced clonogenic growth and migratory properties of ALDHpositive pancreatic cancer cells suggest a key role in the development of metastatic disease that negatively affects the overall survival of patients with pancreatic adenocarcinoma

From high-grade, absence of hormone receptor expression to positive HER2 status and the basal-like molecular subtype, the expression of ALDH1 is in direct relation with undesired

Breast cancer cells with stem-cell-like properties are suggested to be responsible for metastatic spread. Aldehyde dehydrogenase 1 (ALDH1) and cluster of differentiation 44 (CD44) in addition to RhoC GTPase are among the stem cell markers that are expressed by

tumor characteristics in breast cancer (Mieog*, et al.*, 2012).

these cells (Chaterjee & van Golen, 2011).

discovered *cis*-elements linked with cell cycle regulation (Marchitti*, et al.*, 2008).

in some higher mammals, including humans (Fauquier*, et al.*, 2003).

**4. ALDH in cancer and cancer stem cells** 

**4.1. Adenocarcinoma** 

Govindan, 2007).

(Rasheed*, et al.*, 2010).

**4.2. Breast cancer** 

ALDH1A3 deficiency has been shown to play a critical role in cancer by a number of studies. For instance, in human breast cancer MCF-7 cells, ALDH1A3 expression is downregulated, whereas in cultured human colon cancer cells, *ALDH1A3* is one of two genes that are upregulated by induction of wild type *p*53. In mammary tumor-susceptible BALB/cJ mice that are heterozygous for *p*53, *Aldh1a3* is one of five candidate genes located within a region determined for its linkage to mammary tumorigenesis. In mice resistant to induced mammary tumors, (C57BL/6J), *Aldh1a3* is one of the two upregulated genes. *ALDH1A3* is silenced by methylation in gastric cancer cells, whereas in glioblastoma cells, it is triggered by the antitumor agent IL-13 cytotoxin (Marchitti*, et al.*, 2008).
